Objective: To study the effect of simulated ischemia-reperfusion (I/R) on If of sinoatrial node (SAN) cells and the intervention of KATP channel opener Pinacidil. Methods: The SAN cells of the neonatal rats were detac...Objective: To study the effect of simulated ischemia-reperfusion (I/R) on If of sinoatrial node (SAN) cells and the intervention of KATP channel opener Pinacidil. Methods: The SAN cells of the neonatal rats were detached and purified 2 d before the experiment. The experimental animals were randomly divided into the control group, group of simulated I/R, group intervened with KATP channel opener Pinacidil (P+ I/R) and group intervened with KATP channel blocking agent 5-HD (5-HD + P + I/R & 5-HD + I/R). The If density of each group was measured by technique of routine whole cell patch clamp and multiple-catheter perfusion system and the If activated curve in each group was drawn. Results: ①Under different directive potentials, the If density of the SAN cells in I/R group increased significantly, compared with that in the control group ( P < 0.01); that in P + I/R group decreased significantly, compared with that in I/R group ( P < 0.01); the If density values in 5-HD + P + I/R group and 5-HD + I/R group increased significantly, compared with that in P + I/R group, but showed no significant difference with that in I/R group. ②Compared with that in the control group, the If activated curve of the SAN cells moved rightwards under ultimate activating potential, half of which was from - 108.0 ± 12.4 to - 89.5 ± 7.2 mV ( P <0.01); compared with that in I/R group, If activated curve of the SAN cells moved leftwards under ultimate activating potential, half of which was the range from -99.5± 10.8 mV (P<0.05); KATP channel blocking agent 5-HD could block the effect of Pinacdil on If activated curve. Conclusion: KATP channel opener Pinacidil can antagonize the effect of simulated I/R on the If of SAN cells, which may be beneficial to the maintenance of the relative stability of ion steady state and electrophysiological activities under condition of simulated I/R.展开更多
BACKGROUND Transient neonatal diabetes mellitus(TNDM)is a rare form of diabetes mellitus that usually presents within the first 6 mo of life.Patients often enter remission within several months,although relapse can oc...BACKGROUND Transient neonatal diabetes mellitus(TNDM)is a rare form of diabetes mellitus that usually presents within the first 6 mo of life.Patients often enter remission within several months,although relapse can occur later in life.Mutations in the ABCC8 gene,which encodes the sulfonylurea receptor 1 of the ATP-sensitive potassium channel in pancreatic beta cells,are associated with TNDM and permanent neonatal diabetes.This study describes a novel de novo c.3880C>T heterozygous ABCC8 variant that causes TNDM and can be treated with sulfonylurea therapy.CASE SUMMARY We retrospectively analyzed 2 Chinese patients with TNDM who were diagnosed,treated,or referred for follow-up between September 2017 and September 2023.The patients were tested for mutations using targeted next-generation sequencing.Patients with neonatal diabetes mellitus caused by a c.3880C>T heterozygous missense variant in the ABCC8 gene have not been reported before.Both children had an onset of post-infectious diabetic ketoacidosis,which is worth noting.At a follow-up visit after discontinuing insulin injection,oral glyburide was found to be effective with no adverse reactions.CONCLUSION Early genetic testing of neonatal diabetes mellitus aids in accurate diagnosis and treatment and helps avoid daily insulin injections that may cause pain.展开更多
Objective: To study the effect of KATp channel opener and its possible mechanism on the sinoatrial node cells of neonatal rats which were cultured under simulated ischemia-reperfusion. Methods: Freshly isolated sinoat...Objective: To study the effect of KATp channel opener and its possible mechanism on the sinoatrial node cells of neonatal rats which were cultured under simulated ischemia-reperfusion. Methods: Freshly isolated sinoatrial node (SAN) cells of neonatal rats were purified and cultured for 2 d, and then they were randomly divided into the control, simulated ischemia-reperfusion group (I/R group) , group intervened with KATp channel opener pinacidil (P + I/R group), KATP Channel blocking agent 5-HD (5-HD + I/R group) , and group with the 2 agents at same time (5-HD + P + I/R group) . The survival rate of cells was measured by flow cytometry and the content of intracellular calcium in the cells of each group was detected with laser confocal microscopy. Results: ① The survival rate of SAN cells in I/R group [ (51. 79±6. 28)% ] was remarkably significantly lower than in control [ (95. 08±10. 48)% ] (P < 0.001), and very significantly lower than in P + I/R group [ (63. 77±5. 35) % ] (P<0.01), however, those of 5-HD + P + I/R group [(52. 88±6. 25)% ] and 5-HD+I/R group [ (53. 16±5. 35)% ] was significantly lower compared with that in P + I/R group (P <0. 01) ; ② When the average fluorescence intensity of sinoatrial node cells in the control was regarded as 100% , the relative fluorescence intensities of each group were: ( 374±52) % in I/R group, significantly higher than that of control (P <0. 01) ; ( 162±20)% in P + I/R group, declining significantly than that of I/R group (P<0.01); (385?6)% in 5-HD+ P + I/R group and (379±44)% in 5-HD + I/R group, increasing significantly than that of I/R group (P<0.01). Conclusion: ① Simulated ischemia-reperfusion can significantly reduce the survival rate of SAN cells, and can also lead to the overload of intracellular calcium in them.② KATp channel opener, pinacidil, exerts protective effect on the cells under simulated ischemia-reperfusion, which may be associated with the decrease of intracellular calcium loading in them.展开更多
The ATP-sensitive potassium（KATP）channels which extensively distribute in diverse tissues（e.g.vascular smooth muscle,cardiac cells,and pancreas）are well-established for characteristics like vasodilatation,myocardi...The ATP-sensitive potassium（KATP）channels which extensively distribute in diverse tissues（e.g.vascular smooth muscle,cardiac cells,and pancreas）are well-established for characteristics like vasodilatation,myocardial protection against ischemia,and insulin secretion.The aim of this review is to get insight into the novel roles of KATPchannels in Parkinson＇s disease（PD）,with consideration of the specificities KATPchannels in the central nervous system（CNS）, such as the control of neuronal excitability,action potential,mitochondrial function and neurotransmitter release.展开更多
Objective To explore the new stratigies targeting at SUR2B/Kir6.1 subtype against pressure overload-induced heart failure.Methods Pressure overload-induced heart failure was induced in Wistar rat by abdominal aortic b...Objective To explore the new stratigies targeting at SUR2B/Kir6.1 subtype against pressure overload-induced heart failure.Methods Pressure overload-induced heart failure was induced in Wistar rat by abdominal aortic banding(AAB).The effects of natakalim(1,3,9 mg·kg-1·d-1,10 weeks)were assessed on myocardial hypertrophy and heart failure,cardiac histology,vasoactive compounds,and gene expression.Isolated working heart and isolated tail artery helical strips were used to examine the influence of natakalim on heart and resistant vessels.Results Ten weeks after the onset of pressure overload,natakalim therapy potently inhibited cardiac hypertrophy and prevented heart failure.Natakalim inhibited the changes of left ventricular haemodynamic parameters,reversed the increase of heart mass index,left ventricular weight index and lung weight index remarkably.Histological examination demonstrated that there were no significant hypertrophy and fibrosis in hearts of pressure overload rat treated with natakalim.Ultrastructural examination of heart revealed well-organized myofibrils with mitochondria grouped along the periphery of longitudinally oriented fibers in natakalim group rats.The content of serum NO and plasma PGI2 was increased,while that of plasma ET-1 and cardiac tissue hydroxyproline,ANP and BNP mRNA was down-regulated in natakalim-treated rats.Natakalim at concentrations ranging from 0.01-100 μM had no effects on isolated working heart derived from Wistar rats;however,natakalim had endothelium-dependent vasodilation effects on the isolated tail artery helical strips precontracted with NE.Conclusions These results indicate that natakalim improves heart failure due to pressure overload by activating KATP channel SUR2B/Kir6.1 subtype and reversing endothelial dysfunction.展开更多
基金Supported by National Natural Science Foundation of China (No.30070314)
文摘Objective: To study the effect of simulated ischemia-reperfusion (I/R) on If of sinoatrial node (SAN) cells and the intervention of KATP channel opener Pinacidil. Methods: The SAN cells of the neonatal rats were detached and purified 2 d before the experiment. The experimental animals were randomly divided into the control group, group of simulated I/R, group intervened with KATP channel opener Pinacidil (P+ I/R) and group intervened with KATP channel blocking agent 5-HD (5-HD + P + I/R & 5-HD + I/R). The If density of each group was measured by technique of routine whole cell patch clamp and multiple-catheter perfusion system and the If activated curve in each group was drawn. Results: ①Under different directive potentials, the If density of the SAN cells in I/R group increased significantly, compared with that in the control group ( P < 0.01); that in P + I/R group decreased significantly, compared with that in I/R group ( P < 0.01); the If density values in 5-HD + P + I/R group and 5-HD + I/R group increased significantly, compared with that in P + I/R group, but showed no significant difference with that in I/R group. ②Compared with that in the control group, the If activated curve of the SAN cells moved rightwards under ultimate activating potential, half of which was from - 108.0 ± 12.4 to - 89.5 ± 7.2 mV ( P <0.01); compared with that in I/R group, If activated curve of the SAN cells moved leftwards under ultimate activating potential, half of which was the range from -99.5± 10.8 mV (P<0.05); KATP channel blocking agent 5-HD could block the effect of Pinacdil on If activated curve. Conclusion: KATP channel opener Pinacidil can antagonize the effect of simulated I/R on the If of SAN cells, which may be beneficial to the maintenance of the relative stability of ion steady state and electrophysiological activities under condition of simulated I/R.
基金Supported by the Department of Science and Technology of Henan Province,China,No.222102310461。
文摘BACKGROUND Transient neonatal diabetes mellitus(TNDM)is a rare form of diabetes mellitus that usually presents within the first 6 mo of life.Patients often enter remission within several months,although relapse can occur later in life.Mutations in the ABCC8 gene,which encodes the sulfonylurea receptor 1 of the ATP-sensitive potassium channel in pancreatic beta cells,are associated with TNDM and permanent neonatal diabetes.This study describes a novel de novo c.3880C>T heterozygous ABCC8 variant that causes TNDM and can be treated with sulfonylurea therapy.CASE SUMMARY We retrospectively analyzed 2 Chinese patients with TNDM who were diagnosed,treated,or referred for follow-up between September 2017 and September 2023.The patients were tested for mutations using targeted next-generation sequencing.Patients with neonatal diabetes mellitus caused by a c.3880C>T heterozygous missense variant in the ABCC8 gene have not been reported before.Both children had an onset of post-infectious diabetic ketoacidosis,which is worth noting.At a follow-up visit after discontinuing insulin injection,oral glyburide was found to be effective with no adverse reactions.CONCLUSION Early genetic testing of neonatal diabetes mellitus aids in accurate diagnosis and treatment and helps avoid daily insulin injections that may cause pain.
基金Supported by National Natural Science Foundation of China (No. 30070314)
文摘Objective: To study the effect of KATp channel opener and its possible mechanism on the sinoatrial node cells of neonatal rats which were cultured under simulated ischemia-reperfusion. Methods: Freshly isolated sinoatrial node (SAN) cells of neonatal rats were purified and cultured for 2 d, and then they were randomly divided into the control, simulated ischemia-reperfusion group (I/R group) , group intervened with KATp channel opener pinacidil (P + I/R group), KATP Channel blocking agent 5-HD (5-HD + I/R group) , and group with the 2 agents at same time (5-HD + P + I/R group) . The survival rate of cells was measured by flow cytometry and the content of intracellular calcium in the cells of each group was detected with laser confocal microscopy. Results: ① The survival rate of SAN cells in I/R group [ (51. 79±6. 28)% ] was remarkably significantly lower than in control [ (95. 08±10. 48)% ] (P < 0.001), and very significantly lower than in P + I/R group [ (63. 77±5. 35) % ] (P<0.01), however, those of 5-HD + P + I/R group [(52. 88±6. 25)% ] and 5-HD+I/R group [ (53. 16±5. 35)% ] was significantly lower compared with that in P + I/R group (P <0. 01) ; ② When the average fluorescence intensity of sinoatrial node cells in the control was regarded as 100% , the relative fluorescence intensities of each group were: ( 374±52) % in I/R group, significantly higher than that of control (P <0. 01) ; ( 162±20)% in P + I/R group, declining significantly than that of I/R group (P<0.01); (385?6)% in 5-HD+ P + I/R group and (379±44)% in 5-HD + I/R group, increasing significantly than that of I/R group (P<0.01). Conclusion: ① Simulated ischemia-reperfusion can significantly reduce the survival rate of SAN cells, and can also lead to the overload of intracellular calcium in them.② KATp channel opener, pinacidil, exerts protective effect on the cells under simulated ischemia-reperfusion, which may be associated with the decrease of intracellular calcium loading in them.
基金the National Natural Science Foundation of China（No.30700251）；the National Basic Research Development Program of China（No.2006CB500706）；the Young Excellent Scholar（2007-2008）Program of Shanghai Jiaotong University School of Medicine.
文摘The ATP-sensitive potassium（KATP）channels which extensively distribute in diverse tissues（e.g.vascular smooth muscle,cardiac cells,and pancreas）are well-established for characteristics like vasodilatation,myocardial protection against ischemia,and insulin secretion.The aim of this review is to get insight into the novel roles of KATPchannels in Parkinson＇s disease（PD）,with consideration of the specificities KATPchannels in the central nervous system（CNS）, such as the control of neuronal excitability,action potential,mitochondrial function and neurotransmitter release.
文摘Objective To explore the new stratigies targeting at SUR2B/Kir6.1 subtype against pressure overload-induced heart failure.Methods Pressure overload-induced heart failure was induced in Wistar rat by abdominal aortic banding(AAB).The effects of natakalim(1,3,9 mg·kg-1·d-1,10 weeks)were assessed on myocardial hypertrophy and heart failure,cardiac histology,vasoactive compounds,and gene expression.Isolated working heart and isolated tail artery helical strips were used to examine the influence of natakalim on heart and resistant vessels.Results Ten weeks after the onset of pressure overload,natakalim therapy potently inhibited cardiac hypertrophy and prevented heart failure.Natakalim inhibited the changes of left ventricular haemodynamic parameters,reversed the increase of heart mass index,left ventricular weight index and lung weight index remarkably.Histological examination demonstrated that there were no significant hypertrophy and fibrosis in hearts of pressure overload rat treated with natakalim.Ultrastructural examination of heart revealed well-organized myofibrils with mitochondria grouped along the periphery of longitudinally oriented fibers in natakalim group rats.The content of serum NO and plasma PGI2 was increased,while that of plasma ET-1 and cardiac tissue hydroxyproline,ANP and BNP mRNA was down-regulated in natakalim-treated rats.Natakalim at concentrations ranging from 0.01-100 μM had no effects on isolated working heart derived from Wistar rats;however,natakalim had endothelium-dependent vasodilation effects on the isolated tail artery helical strips precontracted with NE.Conclusions These results indicate that natakalim improves heart failure due to pressure overload by activating KATP channel SUR2B/Kir6.1 subtype and reversing endothelial dysfunction.
