To elucidate the mechanism of arrhythmia in healed myocardial infarction (HMI), the changes of action potential duration (APD), transient outward potassium current (I to), delayed rectifier potassium current (I K)...To elucidate the mechanism of arrhythmia in healed myocardial infarction (HMI), the changes of action potential duration (APD), transient outward potassium current (I to), delayed rectifier potassium current (I K) and inward rectifier potassium current (I K1) of left ventricular myocytes in non-infarcted zone of HMI were investigated. Rabbits were randomly assigned into two groups: HMI group, in which animals were subjected to thoracotomy and ligation of the circumflex coronary and sham-operated group, in which rabbits underwent thoracotomy but no conorary ligation. 3 months after the operation, the whole myocyte patch clamp technique was used to record APD, I to, I K, and I K1 of ventricular myocytes in non-infarcted zone.Our results showed that the membrane capacitance was larger in HMI group than in sham-operated group. Action potential duration was significantly lengthened in HMI group and early afterdepolarization (EAD) appeared in HMI group. The densities of I to, I K, tail, and I K1 were reduced significantly in HMI group, from 6.72±0.42 pA/pF, 1.54±0.13 pA/pF and 25.6±2.6 pA/pF in sham-operated group to 4.03±0.33 pA/pF, 1.14±0.11 pA/pF and 17.6 ±2.3 pA/pF, respectively. It is concluded that the reduced densities of I to , I K, tail and I K1 in ventricular myocytes of non-infarcted zone in HMI were responsible for the prolongation of APD and the presentation of EAD which played important roles in the development of malignant arrhythmia in HMI.展开更多
The transmural heterogeneous changes of transient outward potassium currents (Ito) in rabbit hypertrophic cardiaomyocytes and the effects of long-term prophylactic treatment with volsartan were investigated. Rabbits w...The transmural heterogeneous changes of transient outward potassium currents (Ito) in rabbit hypertrophic cardiaomyocytes and the effects of long-term prophylactic treatment with volsartan were investigated. Rabbits were divided into hypertrophy group (left ventricular hypertrophy induced by partial ligation of abdominal aorta), vol-treated group (volsartan was administrated after the ligation), and control group (sham operated). Myocytes were isolated by a two-step enzymatical method. The sub-endocardial (Endo) and sub-epicardium (Epi) tissues were separated from midmyocardium (Mid) with a razor. Whole-cell patch-clamp technique was used to record potassium currents. The results showed that membrane capacitance was larger in hypertrophic cells than those in control and vol-treated cells (P<0.01 vs control cells, n=30). The densities of Ito in hypertrophic cells were reduced by sub-epicardium (Epi) (27.8±2.9) %, midmyocardium (Mid) (41.0±4.7) %, and sub-endocardium (Endo) (20.3±3.4) % compared with those in control cells. The decrease of Ito density was more pronounced in Mid than in Epi and Endo (P<0.01 vs Epi or Endo). There were no significant differences in Ito densities between vol-treated group and control group in three layers separately. In conclusion, volsartan can inhibit the transmural heterogeneous changes of Ito in left ventricular hypertrophic cardiomyocytes in rabbit.展开更多
Background Previous studies demonstrated general anesthetics affect potassium ion channels, which may be one of the mechanisms of general anesthesia. Because the effect of etomidate on potassium channels in rat hippoc...Background Previous studies demonstrated general anesthetics affect potassium ion channels, which may be one of the mechanisms of general anesthesia. Because the effect of etomidate on potassium channels in rat hippocampus which is involved in memory function has not been studied, we investigated the effects of etomidate on both delayed rectifier potassium current （IK（DR）） and transient outward potassium current （I_K（A）） in acutely dissociated rat hippocampal pyramidal neurons.Methods Single rat hippocampal pyramidal neurons from male Wistar rats of 7-10 days were acutely dissociated by enzymatic digestion and mechanical dispersion according to the methods of Kay and Wong with slight modification. Voltage-clamp recordings were performed in the whole-cell patch clamp configuration. Currents were recorded with a List EPC-10 amplifier and data were stored in a computer using Pulse 8.5. Student＇s paired two-tail t test was used for data analysis. Results At the concentration of 100 μmol/L, etomidate significantly inhibited IK（DR） by 49.2% at ＋40 mV when depolarized from -110 mV （P 〈0.01, n=8）, while did not affect IK（A） （/1=8, P 〉0.05）. The IC50value of etomidate for blocking IK（DR）was calculated as 5.4 μmol/L, with a Hill slope of 2.45. At the presence of 10 μmol/L etomidate, the V1/2 of activation curve was shifted from （17.3±1.5） mV to （10.7±9.9） mV （n=8, P 〈0.05）, the V1/2 of inactivation curve was shifted from （-18.3±2.2） mV to （-45.3±9.4） mV （n=8, P 〈0.05）. Etomidate 10 μmol/L shifted both the activation curve and inactivation curve of IK（DR））to negative potential, but mainly affected the inactivation kinetics.Conclusions Etomidate potently inhibited IK（DR） but not IK（A） in rat hippocampal pyramidal neurons. IK（DR） was inhibited by etomidate in a concentration-dependent manner, while IK（A） remained unaffected.展开更多
Background Some studies have confirmed that the right ventricular walls of most rodents, such as canines and humans, have evident transient outward potassium current (I to1) heterogeneity, and this heterogeneity i...Background Some studies have confirmed that the right ventricular walls of most rodents, such as canines and humans, have evident transient outward potassium current (I to1) heterogeneity, and this heterogeneity is closely related to J point elevation, J wave formation, and some ventricular tachycardias such as ventricular fibrillations caused by Brugada syndrome. This study is designed to investigate transmural electrical heterogeneity of the canine right ventricle during repolarization (phase 1) from the viewpoint of 4-aminopyridine sensitive and calcium-independent I to1. Methods Adult canine single right ventricular epicardial (Epi) cells, mid-myocardial (M) cells, and endocardial (Endo) cells were enzymatically dissociated. Whole cell voltage-clamp recordings were made to compare the I to1 values of the three cell types. Results At 37℃ and using 0.2 Hz and +70 mV depolarizing test potentials, the average peak I to1 values of Epi cells and M cells averaged (4070±1720) pA and (3540±1840) pA, respectively. The activated and inactivated Epi and M cells kinetic processes were in accordance with the Boltzmann distribution. Compared with I to1 in Epi cells and M cells, the average peak I to1 in Endo cells was very low, averaged (470±130) pA. Conclusions These results suggest that there are evident differences and potent gradients in I to1 between the three cardiac cell types, especially between Epi and Endo cells. These differences are among the prominent manifestations of right ventricular electrical heterogeneity, and may form an important ionic basis and prerequisite for some malignant arrhythmias in the right ventricle, including those arising from Brugada syndrome and other diseases.展开更多
The effects of La^3＋ on proliferation, cell cycles, apoptosis and ion channels were investigated in mouse embryo fibroblast NIH 3T3 cells and its possible mechanisms were explored. Our data showed that La^3＋ promote...The effects of La^3＋ on proliferation, cell cycles, apoptosis and ion channels were investigated in mouse embryo fibroblast NIH 3T3 cells and its possible mechanisms were explored. Our data showed that La^3＋ promoted cell proliferation with increased S-phase entry and inhibited the outward potassium currents in a concentration-dependent manner in NIH 3T3 cells. La^3＋ and Ca^2＋ had synergistic effect on cell proliferation and cell cycles. It showed that Ca^2＋ was needed for La^3＋ promoted cell cycle progression. Using the whole-cell voltage-clamp technique, we found that La^3＋ blocked the outward potassium current in a Lanthanum ions can increase intracellular Ca^2＋ concentration concentration-dependent manner in NIH 3T3 cells. through inhibition of potassium currents, which induce a series of physiological changes and improve proliferation of cells. This may be one of the molecular mechanisms of lanthanum ions induced cell proliferation. The present work provides a new perspective for understanding the biological and toxicological effects of lanthanum.展开更多
Many rat taste receptor cells conduct action potentials(APs).APs had a mean threshold of -35 mV(n=95 cells)and a spike height of 52mV above threshold in current clamp(hold= -80mV).Aps could be classified into two sign...Many rat taste receptor cells conduct action potentials(APs).APs had a mean threshold of -35 mV(n=95 cells)and a spike height of 52mV above threshold in current clamp(hold= -80mV).Aps could be classified into two significantly different (P<0.001) groups-fast,with short half-time durations and large outward currents (mean1.3 ms and 2.7nA),and slow,with long duration and small outward currents(mean9.2ms and 0. 29nA).AP upstrokes were conducted by TTX-sensitive sodium currents whereas the downstroke by TEA-blockable outward currents. Voltage dependent analysis of outward current separated transient and sustained components.The transient component was specifically blocked by 4-AP(1mmol/L).A calcium-dependent outward component was also revealed modulating voltage and external calcium concentration.The fast recovery phase of the AP appears related the sustained outward current whereas the after hyperpolarization(AHP) was blocked by 4AP suggesting a significant contribution of the transient component.Forskolin (FSK),which elevates cAMP,reversibly blocked the majority of the sustained current without influencing the transient. FSK greatly exaggerated the AHP without changing the spike height or duration. These data suggest that several components of the outward current contribute specifically to the gustatory AP and that the AP may be modulated by cyclic nucleotides.展开更多
The electrophysiological properties of potassium ion channels are regarded as a basic index for determining the functional differentiation of neural stem cells. In this study, neural stem cells from the hippocampus of...The electrophysiological properties of potassium ion channels are regarded as a basic index for determining the functional differentiation of neural stem cells. In this study, neural stem cells from the hippocampus of newborn rats were induced to differentiate with neurotrophic growth factor, and the electrophysiological properties of the voltage-gated potassium ion channels were observed. Immunofluorescence staining showed that the rapidly proliferating neural stem cells formed spheres in vitro that expressed high levels of nestin. The differentiated neurons were shown to express neuron-specific enolase. Flow cytometric analysis revealed that the neural stem cells were actively dividing and the percentage of cells in the S ＋ G2/M phase was high. However, the ratio of cells in the S ＋ G2/M phase decreased obviously as differentiation proceeded. Whole-cell patch-clamp re- cordings revealed apparent changes in potassium ion currents as the neurons differentiated. The potassium ion currents consisted of one transient outward potassium ion current and one delayed rectifier potassium ion current, which were blocked by 4-aminopyridine and tetraethylammonium, respectively. The experimental findings indicate that neural stem cells from newborn rat hippo- campus could be cultured and induced to differentiate into functional neurons under defined condi- tions in vitro. The differentiated neurons expressed two types of outward potassium ion cur＇ents similar to those of mature neurons in vivo.展开更多
To investigate the effect of intedeukin-1β （IL-1β） on IA and IK currents in cultured murine trigeminal ganglion （TG） neurons, whole-cell patch clamp technique was used to record the IA and IK currents before and...To investigate the effect of intedeukin-1β （IL-1β） on IA and IK currents in cultured murine trigeminal ganglion （TG） neurons, whole-cell patch clamp technique was used to record the IA and IK currents before and after 20 ng/mL IL-1β perfusion. Our results showed that 20 ng/mL IL-1β inhibited IA currents （18.3±10.7）% （n=6, P〈0.05）. IL-1β at 20 ng/mL had no effect on G-V curve of IA but moved the H-infinity curve V0.5 from -36.6±6. 1 mV to-42.4±5.2 mV （n=5, P〈0.01）. However, 20 ng/mL IL-1β had effect on neither the amplitude nor the G-V curve of IK. IL-1β was found to selectively inhibit IA current in TG neurons and the effect may contribute to hyperalgesia under various inflammatory conditions.展开更多
Acutely isolated mouse hippocampal CA3 pyramidal neurons were exposed to 3 mT static magnetic field,and the characteristics of transient outward K+ channel were studied using the whole-cell patch-clamp technique.The e...Acutely isolated mouse hippocampal CA3 pyramidal neurons were exposed to 3 mT static magnetic field,and the characteristics of transient outward K+ channel were studied using the whole-cell patch-clamp technique.The experiment revealed that the amplitude of transient outward potassium channel current was reduced.The maximum activated current densities of control group and exposure group were 163.62±20.68 pA/pF and 98.74±16.57 pA/pF(n=12,P<0.01) respectively.The static magnetic field exposure affected the activation and inactivation process of transient outward potassium channel current.Due to the magnetic field exposure,the half-activation voltage of the activation curves changed from 5.59±1.96 mV to 27.87±7.24 mV(n=12,P<0.05) ,and the slope factor changed from 19.43±2.11 mV to 25.87±4.22 mV(n=12,P<0.05) .The half-inactivation voltage of the inactivation curves also changed from-56.09±0.89 mV to-57.16±1.10 mV(n=12,P>0.05) and the slope factor of the inactivation curves from 8.69±0.80 mV to 10.87±1.02 mV(n=12,P<0.05) .The results show that the static magnetic field can change the characteristics of transient outward K+ channel,and affect the physiological functions of neurons.展开更多
We used RNA interference （RNAi） to disrupt synthesis of the cortical neuronal y-aminobutyric acid A receptor （GABAAR） al in rats during development, and measured outward K＋ currents during neuronal electrical act...We used RNA interference （RNAi） to disrupt synthesis of the cortical neuronal y-aminobutyric acid A receptor （GABAAR） al in rats during development, and measured outward K＋ currents during neuronal electrical activity using whole-cell patch-clamp techniques. Three pairs of small interfering RNA （siRNA） for GABAAR al subunit were designed using OligoEngine RNAi software. This siRNA was found to effectively inhibited GABAAR al mRNA expression in cortical neuronal culture in vitro, but did not significantly affect neuronal survival. Outward K^currents were decreased, indicating that GABAAR al subunits in developing neurons participate in neuronal function by regulating outward K＋ current.展开更多
The current difference between male and female rabbit ventricular myocytes was investigated for elucidating the mechanism of longer QT interval and higher incidence of drug-associated torsade de pointes in female rabb...The current difference between male and female rabbit ventricular myocytes was investigated for elucidating the mechanism of longer QT interval and higher incidence of drug-associated torsade de pointes in female rabbits than in male rabbits. Whole cell patch clamp technique was used to record APD, I_to, I_K,tail, I_K1 and I_Ca,L of myocytes from left ventricular apex. There was no difference in the membrane capacitance between male and female rabbit myocytes. APD_90 was longer in female rabbits (560.4±26.5 ms, n=15) than in male ones (489.0±20.7 ms, n=14), P<0.05. In female rabbit myocytes, I_K,tail, I_to, I_K1 and I_Ca,L were 0.71±0.05 pA/pF (n=17), 8.28±1.03 pA/pF (n=18), 24.5±3.6 pA/pF (n=12) and 9.0±2.3 pA/pF (n=15) respectively. In male rabbit myocytes, they were 0.84±0.07 pA/pF (n=18), 8.60±1.20 pA/pF (n=18), 25.9±4.5 pA/pF (n=14) and 9.3±2.6 pA/pF (n=16) respectively. I_K,tail in female rabbits was significantly lower than that of male rabbits (P<0.05), but there was no difference in I_to, I_K1 and I_Ca,L between male rabbits and female rabbits (P>0.05). The lower I_K,tail of female rabbit myocytes may contribute to the longer repolarization and the higher incidence of drug-associated torsade de pointes.展开更多
The effects of levobunolol hydrochlorid (Bun) on the type L calciumchannel currents (Ica) and delayed rectifier potassium channel currents (Ik) in isolated ventricular myocytes of guinea pig were studied by using patc...The effects of levobunolol hydrochlorid (Bun) on the type L calciumchannel currents (Ica) and delayed rectifier potassium channel currents (Ik) in isolated ventricular myocytes of guinea pig were studied by using patch clamp wholecell recording techniques. The results were showed that: 1) Bun caused a dosedependent decrease in Ica and a dose-dependent increase in Ik of the ventricular myocytes.The threshold concentrations of Bun for Ica and Ik were 10-8 mol/L and10-7 mol/L respectively. The maximum effective concentration of Bun for both Ica and Ik was 3 × 10-5 mol/L, and half-maximal concentration was 3 × 10-6 mol/L;2 ) Ik was blocked by 2× 10-6mol/L tetraethylammonium (TEA). A concentration of 3 × 10-6 mol/L Bun showed a decreasing effect on the Ica as revealed by the current-voltage relationship curve, i. e., Bun caused an elevation of the curve; 3)When Ica was blocked by 2 × 10-6 mol/L Isoptin (Verapamil), at a concentrationof 3 × 106- mol/L Bun showed an increasing effect on Ik and the effect could be blocked by TEA. The above-mentioned results indicated that Bun had an inhibito-ry effect on Ica and a fascilitatory effect on Ik The results suggested that themolecular mechanisms of antihypertensive, heart rate slowing and β-receptorblocking effects of Bun might be due to decrease of Ica and increase of Ik.展开更多
By numerical simulations on frequency dependence of the spiking threshold, i.e. on the critical amplitude of periodic stimulus, for a neuron to fire, we find that bushy cells in the cochlear nuclear exhibit frequency ...By numerical simulations on frequency dependence of the spiking threshold, i.e. on the critical amplitude of periodic stimulus, for a neuron to fire, we find that bushy cells in the cochlear nuclear exhibit frequency selec- tivity behaviour. However, the selective frequency band of a bushy cell is far away from that of the preferred spectral range in human and mammal auditory perception. The mechanism underlying this neural activity is also discussed. Further studies show that the ion channel densities have little impact on the selective frequency band of bushy cells. These findings suggest that the neuronal behaviour of frequency selectivity in bushy cells at both the single cell and population levels may be not functionally relevant to frequency discrimination. Our results may reveal a neural hint to the reconsideration on the busily cell functional role in auditory information processing of sound frequency.展开更多
Objectives To evaluate the association between a KCNQ 1 mutation, R259H, and short QT syndrome （SQTS） and to explore the elec- trophysiological mechanisms underlying their association. Methods We performed genetic s...Objectives To evaluate the association between a KCNQ 1 mutation, R259H, and short QT syndrome （SQTS） and to explore the elec- trophysiological mechanisms underlying their association. Methods We performed genetic screening of SQTS genes in 25 probands and their family members （63 patients）. We used direct sequencing to screen the exons and intron-exon boundaries of candidate genes that en- code ion channels which contribute to the repolarization of the ventricular action potential, including KCNQI, KCNH2, KCNE1, KCNE2, KCNJ2, CACNAlc, CACNB2b and CACNA2D1. In one of the 25 SQTS probands screened, we discovered a KCNQ1 mutation, R259H. We cloned R259H and transiently expressed it in HEK-293 cells; then, currents were recorded using whole cell patch clamp techniques. Results R259H-KCNQ 1 showed significantly increased current density, which was approximately 3-fold larger than that of wild type （WT） after a depolarizing pulse at 1 s. The steady state voltage dependence of the activation and inactivation did not show significant differences between the WT and R259H mutation （P 〉 0.05）, whereas the time constant of deactivation was markedly prolonged in the mutant compared with the WT in terms of the test potentials, which indicated that the deactivation of R259H was markedly slower than that of the WT. These results suggested that the R259H mutation can effectively increase the slowly activated delayed rectifier potassium current （Irs） in phase 3 of the cardiac action potential, which may be an infrequent cause of QT interval shortening. Conclusions R259H is a gain-of-function muta- tion of the KCNQ1 channel that is responsible for SQTS2. This is the first time that the R259H mutation was detected in Chinese people.展开更多
Genome-wide studies have reported that Parkinson’s disease is associated with abnormal expression of various growth factors. In this study, male C57 BL/6 mice aged 10 weeks were used to establish Parkinson’s disease...Genome-wide studies have reported that Parkinson’s disease is associated with abnormal expression of various growth factors. In this study, male C57 BL/6 mice aged 10 weeks were used to establish Parkinson’s disease models using an intraperitoneal injection of 60 mg/kg 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. 28 days later, 10 or 100 ng fibroblast growth factor 20 was injected intracerebroventricularly. The electrophysiological changes in the mouse hippocampus were recorded using a full-cell patch clamp. Expression of Kv4.2 in the substantia nigra was analyzed using a western blot assay. Serum malondialdehyde levels were analyzed by enzyme-linked immunosorbent assay. The motor coordination of mice was evaluated using the rotarod test. The results showed that fibroblast growth factor 20 decreased A-type potassium current in neurons of the substantia nigra, increased long-term potentiation amplitude in the hippocampus, and downregulated Kv4.2 expression. A high dose of fibroblast growth factor 20 reduced serum malondialdehyde levels and enhanced the motor coordination of mice. These findings confirm that fibroblast growth factor 20 has a therapeutic effect on the toxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, and its mechanism of action is associated with the inhibition of A-type K+ currents and Kv4.2 expression. All animal procedures were approved by the Animal Care and Use Committee of Qilu Hospital of Shandong University, China in 2017(approval No. KYLL-2017-0012).展开更多
Objective To investigate the alterations of cardiac electrophysiological properties and substantial mechanism and find the stable arrhythmia mouse model in Kunming （KM） and C57BL6/J （C57） mice. Methods Electrocar...Objective To investigate the alterations of cardiac electrophysiological properties and substantial mechanism and find the stable arrhythmia mouse model in Kunming （KM） and C57BL6/J （C57） mice. Methods Electrocardiogram recordings were used to analyze the QT interval in vivo, and mono- phasic action potential of right and left ventricular epicardium was recorded to elicit changes of action potential duration （APD） in conventional and programmed electrical stimulation （PES）. Transient outward potassium current （Its,） was recorded via whole-cell patch-clamp technique in single right and left epicardial myocytes. Results QT interval was prolonged in KM mice relative to C57 mice （62.51±4.47 ms vs. 52.59±4.85 ms, P〈0.05）. The APD at 50% repolarization of the left ventricular epicardium （18.60±0.91 ms vs. 12.90±0.35 ms）, and APDs at 50% （17.31±6.05 ms vs. 12.00±3.24 ms） and 70% repolarization （36.13±5.32 ms vs. 2 1.95±8.06 ms） of the right ventricular epicardium in KM mice were significantly pro- longed compared with C57 mice, respectively （all P〈0.05）. KM mice were more sensitive to PES-induced ventricular tachycardia （25%, 3 of 12 hearts）, and especially to Burst-induced ventricular tachycardia （50%, 6 of 12 hearts） compared with C57 mice, which were 20% （2 of 10 hearts） and 30% （3 of 10 hearts） respec- tively. It,, densities both in the left and right ventricular epicardial myocytes from KM mice were significantly decreased compared with C57 mice, respectively （all P〈0.01）. Conclusion Our data showed that KM mice with tile prolonged QT interval and APD are ruiner- abilities to ventricular arrhythmia, which are attributed to lower Ito densities in ventricular myocytes ob- tained from KM mice than that from C57 mice.展开更多
Objective Abnormal QT prolongation associated with arrhythmias is considered the major cardiac electrical disorder and a significant predictor of mortality in diabetic patients. The precise ionic mechanisms for diabet...Objective Abnormal QT prolongation associated with arrhythmias is considered the major cardiac electrical disorder and a significant predictor of mortality in diabetic patients. The precise ionic mechanisms for diabetic QT prolongation remained unclear. The present study was designed to analyze the changes of ventricular repolarization and the underlying ionic mechanisms in diabetic rabbit hearts. Methods Diabetes was induced by a single injection ofalloxan （145mg/kg, Lv. ）. After the development of diabetes （10 weeks）, ECG was measured. Whole-cell patch-clamp technique was applied to record the action potential duration （APD50, APD90）, slowly activating outward rectifying potassium current （IKs）, L-type calcium current （ICa-L） and inward rectifying potassium current （IK1）. Results The action potential duration （APD50 and APD90） of ventricular myocytes was obviously prolonged from 271.5＋32.3 ms and 347.8＋36.3 ms to 556.6~72.5 ms and 647.9~72.2 ms respectively （P〈 0.05）. Meanwhile the normalized peak current densities of IKs in ventricular myocytes investigated by whole-cell patch clamp was smaller in diabetic rabbits than that in control group at test potential of＋50mV （1.27~0.20 pA/pF vs 3.08~0.67 pA/pF, P〈0.05）. And the density of the ICa-L was increased apparently at the test potential of 10 mV （-2.67~0.41 pA/pF vs -5.404-1.08 pA/pF, P〈0.05）. Conclusion Ventricular repolarization was prolonged in diabetic rabbits, it may be partly due to the increased L-type calcium current and reduced slow delayed rectifier K＋ current （IKs） （J Geriatr Cardio12010; 7：25-29）.展开更多
The effects of a new O-superfamily conotoxin, SO3, on sodium current (INa), transient A-type potassium currents (IA),and delayed rectified potassium currents (IK), were examined in cultured rat hippocampal neurons usi...The effects of a new O-superfamily conotoxin, SO3, on sodium current (INa), transient A-type potassium currents (IA),and delayed rectified potassium currents (IK), were examined in cultured rat hippocampal neurons using the whole-cell patch clamp technique. Addition of SO3 caused a concentration-dependent, rapidly developing, and reversible inhibition of voltage-activated currents. The IC50 values for the blockage of INa , IA, and IK were calculated as 0.49, 33.9, and 7.6 mmol/L, respectively. The determined Hill coefficients were 1.7, 0.6, and 1.2, respectively. These results indicate that SO3 can selectively inhibit neuronal sodium and potassium currents.展开更多
Objective： To study the effect of Xinjining extract （心悸宁, XJN） on inward rectifier potassium current （IKI） in ventricular myocyte （VMC） of guinea pigs and its anti-arrhythmic mechanism on ion channel level. ...Objective： To study the effect of Xinjining extract （心悸宁, XJN） on inward rectifier potassium current （IKI） in ventricular myocyte （VMC） of guinea pigs and its anti-arrhythmic mechanism on ion channel level. Methods： Single VMC was enzymatically isolated by zymolisis, and whole-cell patch clamp recording technique was used to record the Ikl in VMC irrigated with XJN of different concentrations （1.25, 2.50, 5.00 g/L; six samples for each）. The stable current and conductance of the inward component of IK1 as well as the outward component of peak IK1 and conductance of it accordingly was recorded when the test voltage was set on -110 mV. Results： The suppressive rate of XJN on the inward component of IK1 was 9.54% ± 5.81%, 34.82% ± 15.03%, and 59.52% ± 25.58% with a concentration of 1.25, 2.50, and 5.00 g/L, respectively, and that for the outward component of peak IK1 was 23.94%± 7.45%, 52.98%± 19.62%, and 71.42% ± 23.01%, respectively （all P〈0.05）. Moreover, different concentrations of XJN also showed effects for reducing IK1 conductance. Conclusion： XJN has inhibitory effect on IK1in guinea pig＇s VMC, and that of the same concentration shows stronger inhibition on outward component than on inward component, which may be one of the mechanisms of its anti-arrhythmic effect.展开更多
Objective Catecholamines antagonize the clinical efficacy of pure class Ⅲ antiarrhythmic agents in vivo. The antiarrhythmic agent d, l sotalol has β adrenergic blocking properties and class Ⅲ activity. However, ...Objective Catecholamines antagonize the clinical efficacy of pure class Ⅲ antiarrhythmic agents in vivo. The antiarrhythmic agent d, l sotalol has β adrenergic blocking properties and class Ⅲ activity. However, its d isomer without β blockade has been shown to exert significant proarrhythmia. To determine the role of β adrenergic blocking properties of d, l sotalol on its antiarrhythmic effect, we compared the effects of d, l sotalol and d sotalol on delayed rectifier K + outward current in the presence of isoproterenol at different concentrations. Methods Time dependent delayed rectifier K + outward currents, I K (I Kr and I Ks ) and tail current (I K tail ) were measured in isolated guinea pig myocytes using the whole cell configuration of the patch clamp technique. Currents were measured in response to 300 ms depolarizing pulses from a holding potential of Department of Cardiology, University Hospital Heidelberg, Germany (Yao XZ, Yannoulis NC, Kiehn J and Brachmann J) 40 mV in three experimental protocols [control, isoproterenol (10 9 -10 6 mol/L), and isoproterenol (10 9 -10 6 mol/L) plus either d, l sotalol (10 4 mol/L) or d sotalol (10 4 mol/L)]. I K tail currents were measured upon repolarization to 40 mV. Results Isoproterenol significantly inreased I K and I K tail in a concentration dependent manner. I K was significantly amplified in the presence of isoproterenol (10 9 -10 6 mol/L) plus d sotalol. At 10 8 mol/L isoproterenol, I K was increased by 92.3%±23.7% before and 54.3%±13.4% after d sotalol. In contrast, d, l sotalol strongly suppressed the effect of isoproterenol on I K, and compared to control, I K was decreased by 35.6%±8.1% at 10 8 mol/L isoproterenol. Conclusions The β adrenergic blocking property of d, l sotalol maintains delayed rectifier K + outward current block in the presence of isoproterenol in guinea pig myocytes. This may result in its supperior antiarrhythmic efficacy compared to d sotalol.展开更多
文摘To elucidate the mechanism of arrhythmia in healed myocardial infarction (HMI), the changes of action potential duration (APD), transient outward potassium current (I to), delayed rectifier potassium current (I K) and inward rectifier potassium current (I K1) of left ventricular myocytes in non-infarcted zone of HMI were investigated. Rabbits were randomly assigned into two groups: HMI group, in which animals were subjected to thoracotomy and ligation of the circumflex coronary and sham-operated group, in which rabbits underwent thoracotomy but no conorary ligation. 3 months after the operation, the whole myocyte patch clamp technique was used to record APD, I to, I K, and I K1 of ventricular myocytes in non-infarcted zone.Our results showed that the membrane capacitance was larger in HMI group than in sham-operated group. Action potential duration was significantly lengthened in HMI group and early afterdepolarization (EAD) appeared in HMI group. The densities of I to, I K, tail, and I K1 were reduced significantly in HMI group, from 6.72±0.42 pA/pF, 1.54±0.13 pA/pF and 25.6±2.6 pA/pF in sham-operated group to 4.03±0.33 pA/pF, 1.14±0.11 pA/pF and 17.6 ±2.3 pA/pF, respectively. It is concluded that the reduced densities of I to , I K, tail and I K1 in ventricular myocytes of non-infarcted zone in HMI were responsible for the prolongation of APD and the presentation of EAD which played important roles in the development of malignant arrhythmia in HMI.
文摘The transmural heterogeneous changes of transient outward potassium currents (Ito) in rabbit hypertrophic cardiaomyocytes and the effects of long-term prophylactic treatment with volsartan were investigated. Rabbits were divided into hypertrophy group (left ventricular hypertrophy induced by partial ligation of abdominal aorta), vol-treated group (volsartan was administrated after the ligation), and control group (sham operated). Myocytes were isolated by a two-step enzymatical method. The sub-endocardial (Endo) and sub-epicardium (Epi) tissues were separated from midmyocardium (Mid) with a razor. Whole-cell patch-clamp technique was used to record potassium currents. The results showed that membrane capacitance was larger in hypertrophic cells than those in control and vol-treated cells (P<0.01 vs control cells, n=30). The densities of Ito in hypertrophic cells were reduced by sub-epicardium (Epi) (27.8±2.9) %, midmyocardium (Mid) (41.0±4.7) %, and sub-endocardium (Endo) (20.3±3.4) % compared with those in control cells. The decrease of Ito density was more pronounced in Mid than in Epi and Endo (P<0.01 vs Epi or Endo). There were no significant differences in Ito densities between vol-treated group and control group in three layers separately. In conclusion, volsartan can inhibit the transmural heterogeneous changes of Ito in left ventricular hypertrophic cardiomyocytes in rabbit.
基金This study was supported by a grant from the National Nature Science Foundation of China （No. 30672030）.
文摘Background Previous studies demonstrated general anesthetics affect potassium ion channels, which may be one of the mechanisms of general anesthesia. Because the effect of etomidate on potassium channels in rat hippocampus which is involved in memory function has not been studied, we investigated the effects of etomidate on both delayed rectifier potassium current （IK（DR）） and transient outward potassium current （I_K（A）） in acutely dissociated rat hippocampal pyramidal neurons.Methods Single rat hippocampal pyramidal neurons from male Wistar rats of 7-10 days were acutely dissociated by enzymatic digestion and mechanical dispersion according to the methods of Kay and Wong with slight modification. Voltage-clamp recordings were performed in the whole-cell patch clamp configuration. Currents were recorded with a List EPC-10 amplifier and data were stored in a computer using Pulse 8.5. Student＇s paired two-tail t test was used for data analysis. Results At the concentration of 100 μmol/L, etomidate significantly inhibited IK（DR） by 49.2% at ＋40 mV when depolarized from -110 mV （P 〈0.01, n=8）, while did not affect IK（A） （/1=8, P 〉0.05）. The IC50value of etomidate for blocking IK（DR）was calculated as 5.4 μmol/L, with a Hill slope of 2.45. At the presence of 10 μmol/L etomidate, the V1/2 of activation curve was shifted from （17.3±1.5） mV to （10.7±9.9） mV （n=8, P 〈0.05）, the V1/2 of inactivation curve was shifted from （-18.3±2.2） mV to （-45.3±9.4） mV （n=8, P 〈0.05）. Etomidate 10 μmol/L shifted both the activation curve and inactivation curve of IK（DR））to negative potential, but mainly affected the inactivation kinetics.Conclusions Etomidate potently inhibited IK（DR） but not IK（A） in rat hippocampal pyramidal neurons. IK（DR） was inhibited by etomidate in a concentration-dependent manner, while IK（A） remained unaffected.
文摘Background Some studies have confirmed that the right ventricular walls of most rodents, such as canines and humans, have evident transient outward potassium current (I to1) heterogeneity, and this heterogeneity is closely related to J point elevation, J wave formation, and some ventricular tachycardias such as ventricular fibrillations caused by Brugada syndrome. This study is designed to investigate transmural electrical heterogeneity of the canine right ventricle during repolarization (phase 1) from the viewpoint of 4-aminopyridine sensitive and calcium-independent I to1. Methods Adult canine single right ventricular epicardial (Epi) cells, mid-myocardial (M) cells, and endocardial (Endo) cells were enzymatically dissociated. Whole cell voltage-clamp recordings were made to compare the I to1 values of the three cell types. Results At 37℃ and using 0.2 Hz and +70 mV depolarizing test potentials, the average peak I to1 values of Epi cells and M cells averaged (4070±1720) pA and (3540±1840) pA, respectively. The activated and inactivated Epi and M cells kinetic processes were in accordance with the Boltzmann distribution. Compared with I to1 in Epi cells and M cells, the average peak I to1 in Endo cells was very low, averaged (470±130) pA. Conclusions These results suggest that there are evident differences and potent gradients in I to1 between the three cardiac cell types, especially between Epi and Endo cells. These differences are among the prominent manifestations of right ventricular electrical heterogeneity, and may form an important ionic basis and prerequisite for some malignant arrhythmias in the right ventricle, including those arising from Brugada syndrome and other diseases.
基金Project supported by the National Natural Science Foundation of China （Nos. 20637010, 41072265）, Shanxi Provincial Natural Science Foundation for Youth （No. 2007021010） and the Doctoral Scientific Research Foundation of Taiyuan University of Science and Technology （No. 20102027）.
文摘The effects of La^3＋ on proliferation, cell cycles, apoptosis and ion channels were investigated in mouse embryo fibroblast NIH 3T3 cells and its possible mechanisms were explored. Our data showed that La^3＋ promoted cell proliferation with increased S-phase entry and inhibited the outward potassium currents in a concentration-dependent manner in NIH 3T3 cells. La^3＋ and Ca^2＋ had synergistic effect on cell proliferation and cell cycles. It showed that Ca^2＋ was needed for La^3＋ promoted cell cycle progression. Using the whole-cell voltage-clamp technique, we found that La^3＋ blocked the outward potassium current in a Lanthanum ions can increase intracellular Ca^2＋ concentration concentration-dependent manner in NIH 3T3 cells. through inhibition of potassium currents, which induce a series of physiological changes and improve proliferation of cells. This may be one of the molecular mechanisms of lanthanum ions induced cell proliferation. The present work provides a new perspective for understanding the biological and toxicological effects of lanthanum.
文摘Many rat taste receptor cells conduct action potentials(APs).APs had a mean threshold of -35 mV(n=95 cells)and a spike height of 52mV above threshold in current clamp(hold= -80mV).Aps could be classified into two significantly different (P<0.001) groups-fast,with short half-time durations and large outward currents (mean1.3 ms and 2.7nA),and slow,with long duration and small outward currents(mean9.2ms and 0. 29nA).AP upstrokes were conducted by TTX-sensitive sodium currents whereas the downstroke by TEA-blockable outward currents. Voltage dependent analysis of outward current separated transient and sustained components.The transient component was specifically blocked by 4-AP(1mmol/L).A calcium-dependent outward component was also revealed modulating voltage and external calcium concentration.The fast recovery phase of the AP appears related the sustained outward current whereas the after hyperpolarization(AHP) was blocked by 4AP suggesting a significant contribution of the transient component.Forskolin (FSK),which elevates cAMP,reversibly blocked the majority of the sustained current without influencing the transient. FSK greatly exaggerated the AHP without changing the spike height or duration. These data suggest that several components of the outward current contribute specifically to the gustatory AP and that the AP may be modulated by cyclic nucleotides.
基金supported by the National Natural Science Foundation of China,No.31000514the Scientific Research Project for Talent with High Education of Xinxiang Medical University,No.2007502002
文摘The electrophysiological properties of potassium ion channels are regarded as a basic index for determining the functional differentiation of neural stem cells. In this study, neural stem cells from the hippocampus of newborn rats were induced to differentiate with neurotrophic growth factor, and the electrophysiological properties of the voltage-gated potassium ion channels were observed. Immunofluorescence staining showed that the rapidly proliferating neural stem cells formed spheres in vitro that expressed high levels of nestin. The differentiated neurons were shown to express neuron-specific enolase. Flow cytometric analysis revealed that the neural stem cells were actively dividing and the percentage of cells in the S ＋ G2/M phase was high. However, the ratio of cells in the S ＋ G2/M phase decreased obviously as differentiation proceeded. Whole-cell patch-clamp re- cordings revealed apparent changes in potassium ion currents as the neurons differentiated. The potassium ion currents consisted of one transient outward potassium ion current and one delayed rectifier potassium ion current, which were blocked by 4-aminopyridine and tetraethylammonium, respectively. The experimental findings indicate that neural stem cells from newborn rat hippo- campus could be cultured and induced to differentiate into functional neurons under defined condi- tions in vitro. The differentiated neurons expressed two types of outward potassium ion cur＇ents similar to those of mature neurons in vivo.
基金The project was supported by a grant from the National Natural Sciences Foundation of China (No. 30271500)
文摘To investigate the effect of intedeukin-1β （IL-1β） on IA and IK currents in cultured murine trigeminal ganglion （TG） neurons, whole-cell patch clamp technique was used to record the IA and IK currents before and after 20 ng/mL IL-1β perfusion. Our results showed that 20 ng/mL IL-1β inhibited IA currents （18.3±10.7）% （n=6, P〈0.05）. IL-1β at 20 ng/mL had no effect on G-V curve of IA but moved the H-infinity curve V0.5 from -36.6±6. 1 mV to-42.4±5.2 mV （n=5, P〈0.01）. However, 20 ng/mL IL-1β had effect on neither the amplitude nor the G-V curve of IK. IL-1β was found to selectively inhibit IA current in TG neurons and the effect may contribute to hyperalgesia under various inflammatory conditions.
基金Supported by National Natural Science Foundation of China(No. 60674111)
文摘Acutely isolated mouse hippocampal CA3 pyramidal neurons were exposed to 3 mT static magnetic field,and the characteristics of transient outward K+ channel were studied using the whole-cell patch-clamp technique.The experiment revealed that the amplitude of transient outward potassium channel current was reduced.The maximum activated current densities of control group and exposure group were 163.62±20.68 pA/pF and 98.74±16.57 pA/pF(n=12,P<0.01) respectively.The static magnetic field exposure affected the activation and inactivation process of transient outward potassium channel current.Due to the magnetic field exposure,the half-activation voltage of the activation curves changed from 5.59±1.96 mV to 27.87±7.24 mV(n=12,P<0.05) ,and the slope factor changed from 19.43±2.11 mV to 25.87±4.22 mV(n=12,P<0.05) .The half-inactivation voltage of the inactivation curves also changed from-56.09±0.89 mV to-57.16±1.10 mV(n=12,P>0.05) and the slope factor of the inactivation curves from 8.69±0.80 mV to 10.87±1.02 mV(n=12,P<0.05) .The results show that the static magnetic field can change the characteristics of transient outward K+ channel,and affect the physiological functions of neurons.
基金the National Natural Science Foundation for Youth, No. 30400483
文摘We used RNA interference （RNAi） to disrupt synthesis of the cortical neuronal y-aminobutyric acid A receptor （GABAAR） al in rats during development, and measured outward K＋ currents during neuronal electrical activity using whole-cell patch-clamp techniques. Three pairs of small interfering RNA （siRNA） for GABAAR al subunit were designed using OligoEngine RNAi software. This siRNA was found to effectively inhibited GABAAR al mRNA expression in cortical neuronal culture in vitro, but did not significantly affect neuronal survival. Outward K^currents were decreased, indicating that GABAAR al subunits in developing neurons participate in neuronal function by regulating outward K＋ current.
文摘The current difference between male and female rabbit ventricular myocytes was investigated for elucidating the mechanism of longer QT interval and higher incidence of drug-associated torsade de pointes in female rabbits than in male rabbits. Whole cell patch clamp technique was used to record APD, I_to, I_K,tail, I_K1 and I_Ca,L of myocytes from left ventricular apex. There was no difference in the membrane capacitance between male and female rabbit myocytes. APD_90 was longer in female rabbits (560.4±26.5 ms, n=15) than in male ones (489.0±20.7 ms, n=14), P<0.05. In female rabbit myocytes, I_K,tail, I_to, I_K1 and I_Ca,L were 0.71±0.05 pA/pF (n=17), 8.28±1.03 pA/pF (n=18), 24.5±3.6 pA/pF (n=12) and 9.0±2.3 pA/pF (n=15) respectively. In male rabbit myocytes, they were 0.84±0.07 pA/pF (n=18), 8.60±1.20 pA/pF (n=18), 25.9±4.5 pA/pF (n=14) and 9.3±2.6 pA/pF (n=16) respectively. I_K,tail in female rabbits was significantly lower than that of male rabbits (P<0.05), but there was no difference in I_to, I_K1 and I_Ca,L between male rabbits and female rabbits (P>0.05). The lower I_K,tail of female rabbit myocytes may contribute to the longer repolarization and the higher incidence of drug-associated torsade de pointes.
文摘The effects of levobunolol hydrochlorid (Bun) on the type L calciumchannel currents (Ica) and delayed rectifier potassium channel currents (Ik) in isolated ventricular myocytes of guinea pig were studied by using patch clamp wholecell recording techniques. The results were showed that: 1) Bun caused a dosedependent decrease in Ica and a dose-dependent increase in Ik of the ventricular myocytes.The threshold concentrations of Bun for Ica and Ik were 10-8 mol/L and10-7 mol/L respectively. The maximum effective concentration of Bun for both Ica and Ik was 3 × 10-5 mol/L, and half-maximal concentration was 3 × 10-6 mol/L;2 ) Ik was blocked by 2× 10-6mol/L tetraethylammonium (TEA). A concentration of 3 × 10-6 mol/L Bun showed a decreasing effect on the Ica as revealed by the current-voltage relationship curve, i. e., Bun caused an elevation of the curve; 3)When Ica was blocked by 2 × 10-6 mol/L Isoptin (Verapamil), at a concentrationof 3 × 106- mol/L Bun showed an increasing effect on Ik and the effect could be blocked by TEA. The above-mentioned results indicated that Bun had an inhibito-ry effect on Ica and a fascilitatory effect on Ik The results suggested that themolecular mechanisms of antihypertensive, heart rate slowing and β-receptorblocking effects of Bun might be due to decrease of Ica and increase of Ik.
文摘By numerical simulations on frequency dependence of the spiking threshold, i.e. on the critical amplitude of periodic stimulus, for a neuron to fire, we find that bushy cells in the cochlear nuclear exhibit frequency selec- tivity behaviour. However, the selective frequency band of a bushy cell is far away from that of the preferred spectral range in human and mammal auditory perception. The mechanism underlying this neural activity is also discussed. Further studies show that the ion channel densities have little impact on the selective frequency band of bushy cells. These findings suggest that the neuronal behaviour of frequency selectivity in bushy cells at both the single cell and population levels may be not functionally relevant to frequency discrimination. Our results may reveal a neural hint to the reconsideration on the busily cell functional role in auditory information processing of sound frequency.
基金grants obtained from the National Natural Science Foundation of China （No.： 81170177, 81030002） and science and Technology De- partment of Gansu Province Project （145RJZ104）.
文摘Objectives To evaluate the association between a KCNQ 1 mutation, R259H, and short QT syndrome （SQTS） and to explore the elec- trophysiological mechanisms underlying their association. Methods We performed genetic screening of SQTS genes in 25 probands and their family members （63 patients）. We used direct sequencing to screen the exons and intron-exon boundaries of candidate genes that en- code ion channels which contribute to the repolarization of the ventricular action potential, including KCNQI, KCNH2, KCNE1, KCNE2, KCNJ2, CACNAlc, CACNB2b and CACNA2D1. In one of the 25 SQTS probands screened, we discovered a KCNQ1 mutation, R259H. We cloned R259H and transiently expressed it in HEK-293 cells; then, currents were recorded using whole cell patch clamp techniques. Results R259H-KCNQ 1 showed significantly increased current density, which was approximately 3-fold larger than that of wild type （WT） after a depolarizing pulse at 1 s. The steady state voltage dependence of the activation and inactivation did not show significant differences between the WT and R259H mutation （P 〉 0.05）, whereas the time constant of deactivation was markedly prolonged in the mutant compared with the WT in terms of the test potentials, which indicated that the deactivation of R259H was markedly slower than that of the WT. These results suggested that the R259H mutation can effectively increase the slowly activated delayed rectifier potassium current （Irs） in phase 3 of the cardiac action potential, which may be an infrequent cause of QT interval shortening. Conclusions R259H is a gain-of-function muta- tion of the KCNQ1 channel that is responsible for SQTS2. This is the first time that the R259H mutation was detected in Chinese people.
文摘Genome-wide studies have reported that Parkinson’s disease is associated with abnormal expression of various growth factors. In this study, male C57 BL/6 mice aged 10 weeks were used to establish Parkinson’s disease models using an intraperitoneal injection of 60 mg/kg 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. 28 days later, 10 or 100 ng fibroblast growth factor 20 was injected intracerebroventricularly. The electrophysiological changes in the mouse hippocampus were recorded using a full-cell patch clamp. Expression of Kv4.2 in the substantia nigra was analyzed using a western blot assay. Serum malondialdehyde levels were analyzed by enzyme-linked immunosorbent assay. The motor coordination of mice was evaluated using the rotarod test. The results showed that fibroblast growth factor 20 decreased A-type potassium current in neurons of the substantia nigra, increased long-term potentiation amplitude in the hippocampus, and downregulated Kv4.2 expression. A high dose of fibroblast growth factor 20 reduced serum malondialdehyde levels and enhanced the motor coordination of mice. These findings confirm that fibroblast growth factor 20 has a therapeutic effect on the toxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, and its mechanism of action is associated with the inhibition of A-type K+ currents and Kv4.2 expression. All animal procedures were approved by the Animal Care and Use Committee of Qilu Hospital of Shandong University, China in 2017(approval No. KYLL-2017-0012).
基金Supported by the National Natural Science Foundation of China(81070142)Natural Science Foundation of Hubei Province (2011CDB504)
文摘Objective To investigate the alterations of cardiac electrophysiological properties and substantial mechanism and find the stable arrhythmia mouse model in Kunming （KM） and C57BL6/J （C57） mice. Methods Electrocardiogram recordings were used to analyze the QT interval in vivo, and mono- phasic action potential of right and left ventricular epicardium was recorded to elicit changes of action potential duration （APD） in conventional and programmed electrical stimulation （PES）. Transient outward potassium current （Its,） was recorded via whole-cell patch-clamp technique in single right and left epicardial myocytes. Results QT interval was prolonged in KM mice relative to C57 mice （62.51±4.47 ms vs. 52.59±4.85 ms, P〈0.05）. The APD at 50% repolarization of the left ventricular epicardium （18.60±0.91 ms vs. 12.90±0.35 ms）, and APDs at 50% （17.31±6.05 ms vs. 12.00±3.24 ms） and 70% repolarization （36.13±5.32 ms vs. 2 1.95±8.06 ms） of the right ventricular epicardium in KM mice were significantly pro- longed compared with C57 mice, respectively （all P〈0.05）. KM mice were more sensitive to PES-induced ventricular tachycardia （25%, 3 of 12 hearts）, and especially to Burst-induced ventricular tachycardia （50%, 6 of 12 hearts） compared with C57 mice, which were 20% （2 of 10 hearts） and 30% （3 of 10 hearts） respec- tively. It,, densities both in the left and right ventricular epicardial myocytes from KM mice were significantly decreased compared with C57 mice, respectively （all P〈0.01）. Conclusion Our data showed that KM mice with tile prolonged QT interval and APD are ruiner- abilities to ventricular arrhythmia, which are attributed to lower Ito densities in ventricular myocytes ob- tained from KM mice than that from C57 mice.
基金This work was supported by the National Natural Science Foundation of China （30600253）, Min＆try of Edu- cation Key Project （207031） and Scientific Research Fundation for the Returned Chinese Scholars of Heilongjiang Province of China （LC07C20）.
文摘Objective Abnormal QT prolongation associated with arrhythmias is considered the major cardiac electrical disorder and a significant predictor of mortality in diabetic patients. The precise ionic mechanisms for diabetic QT prolongation remained unclear. The present study was designed to analyze the changes of ventricular repolarization and the underlying ionic mechanisms in diabetic rabbit hearts. Methods Diabetes was induced by a single injection ofalloxan （145mg/kg, Lv. ）. After the development of diabetes （10 weeks）, ECG was measured. Whole-cell patch-clamp technique was applied to record the action potential duration （APD50, APD90）, slowly activating outward rectifying potassium current （IKs）, L-type calcium current （ICa-L） and inward rectifying potassium current （IK1）. Results The action potential duration （APD50 and APD90） of ventricular myocytes was obviously prolonged from 271.5＋32.3 ms and 347.8＋36.3 ms to 556.6~72.5 ms and 647.9~72.2 ms respectively （P〈 0.05）. Meanwhile the normalized peak current densities of IKs in ventricular myocytes investigated by whole-cell patch clamp was smaller in diabetic rabbits than that in control group at test potential of＋50mV （1.27~0.20 pA/pF vs 3.08~0.67 pA/pF, P〈0.05）. And the density of the ICa-L was increased apparently at the test potential of 10 mV （-2.67~0.41 pA/pF vs -5.404-1.08 pA/pF, P〈0.05）. Conclusion Ventricular repolarization was prolonged in diabetic rabbits, it may be partly due to the increased L-type calcium current and reduced slow delayed rectifier K＋ current （IKs） （J Geriatr Cardio12010; 7：25-29）.
基金the National Ocean High-Tech Foundation of China (No. 819-06-04)
文摘The effects of a new O-superfamily conotoxin, SO3, on sodium current (INa), transient A-type potassium currents (IA),and delayed rectified potassium currents (IK), were examined in cultured rat hippocampal neurons using the whole-cell patch clamp technique. Addition of SO3 caused a concentration-dependent, rapidly developing, and reversible inhibition of voltage-activated currents. The IC50 values for the blockage of INa , IA, and IK were calculated as 0.49, 33.9, and 7.6 mmol/L, respectively. The determined Hill coefficients were 1.7, 0.6, and 1.2, respectively. These results indicate that SO3 can selectively inhibit neuronal sodium and potassium currents.
基金Supported by the Fundfor Innovation of Phenomof Henan Province(No.0521002400)
文摘Objective： To study the effect of Xinjining extract （心悸宁, XJN） on inward rectifier potassium current （IKI） in ventricular myocyte （VMC） of guinea pigs and its anti-arrhythmic mechanism on ion channel level. Methods： Single VMC was enzymatically isolated by zymolisis, and whole-cell patch clamp recording technique was used to record the Ikl in VMC irrigated with XJN of different concentrations （1.25, 2.50, 5.00 g/L; six samples for each）. The stable current and conductance of the inward component of IK1 as well as the outward component of peak IK1 and conductance of it accordingly was recorded when the test voltage was set on -110 mV. Results： The suppressive rate of XJN on the inward component of IK1 was 9.54% ± 5.81%, 34.82% ± 15.03%, and 59.52% ± 25.58% with a concentration of 1.25, 2.50, and 5.00 g/L, respectively, and that for the outward component of peak IK1 was 23.94%± 7.45%, 52.98%± 19.62%, and 71.42% ± 23.01%, respectively （all P〈0.05）. Moreover, different concentrations of XJN also showed effects for reducing IK1 conductance. Conclusion： XJN has inhibitory effect on IK1in guinea pig＇s VMC, and that of the same concentration shows stronger inhibition on outward component than on inward component, which may be one of the mechanisms of its anti-arrhythmic effect.
文摘Objective Catecholamines antagonize the clinical efficacy of pure class Ⅲ antiarrhythmic agents in vivo. The antiarrhythmic agent d, l sotalol has β adrenergic blocking properties and class Ⅲ activity. However, its d isomer without β blockade has been shown to exert significant proarrhythmia. To determine the role of β adrenergic blocking properties of d, l sotalol on its antiarrhythmic effect, we compared the effects of d, l sotalol and d sotalol on delayed rectifier K + outward current in the presence of isoproterenol at different concentrations. Methods Time dependent delayed rectifier K + outward currents, I K (I Kr and I Ks ) and tail current (I K tail ) were measured in isolated guinea pig myocytes using the whole cell configuration of the patch clamp technique. Currents were measured in response to 300 ms depolarizing pulses from a holding potential of Department of Cardiology, University Hospital Heidelberg, Germany (Yao XZ, Yannoulis NC, Kiehn J and Brachmann J) 40 mV in three experimental protocols [control, isoproterenol (10 9 -10 6 mol/L), and isoproterenol (10 9 -10 6 mol/L) plus either d, l sotalol (10 4 mol/L) or d sotalol (10 4 mol/L)]. I K tail currents were measured upon repolarization to 40 mV. Results Isoproterenol significantly inreased I K and I K tail in a concentration dependent manner. I K was significantly amplified in the presence of isoproterenol (10 9 -10 6 mol/L) plus d sotalol. At 10 8 mol/L isoproterenol, I K was increased by 92.3%±23.7% before and 54.3%±13.4% after d sotalol. In contrast, d, l sotalol strongly suppressed the effect of isoproterenol on I K, and compared to control, I K was decreased by 35.6%±8.1% at 10 8 mol/L isoproterenol. Conclusions The β adrenergic blocking property of d, l sotalol maintains delayed rectifier K + outward current block in the presence of isoproterenol in guinea pig myocytes. This may result in its supperior antiarrhythmic efficacy compared to d sotalol.
