摘要
为研究东亚钳蝎毒素BmkTXKβ对家兔心房肌单细胞电生理特征的影响 ,应用全细胞膜片钳技术记录各项钾电流和动作电位。结果 :BmkTXKβ呈浓度依赖性地延长动作电位时程 (APD2 0 、APD50 和APD90 ) ,但对动作电位幅度 (APA) ,静息膜电位 (RMP)和 0相最大除极速度 (Vmax)无明显影响 (n =9)。在刺激电压 +5 0mV时 1μmol/L的BmkTXKβ使心房肌细胞瞬间外向钾电流 (Ito)从 13.6 3± 0 .87pA/pF减少到 7.98± 0 .78pA/pF ,抑制率为 41.4%(n=10 ,P <0 .0 1)。同时 ,这种作用具有显著的浓度依赖性 ,抑制 5 0 %的电流所需浓度 (IC50 )的均值为 0 .95 μmol/L。BmkTXKβ可抑制延迟整流性钾电流 (IK) ,表现为剂量依赖性阻断的形式。 10 μmol/L时 (刺激电压 +70mV) ,它对IK的抑制率为 39.3 %(从 5 .86± 0 .6 4pA/pF降到 3 .5 6± 0 .5 8pA/pF ,n =6 ,P <0 .0 5 )。IC50 的均值为 2 .76 μmol/L。但BmkTXKβ对内向整流钾电流 (IK1)的电流幅值及其反转电位基本无影响 (n =6 ,P >0 .0 5 )。结论 :BmkTXKβ阻断Ito和IK 等与心脏复极相关的钾离子通道 ,且能在多个环节显著延长APD。
This study is to investigate the effect of BmkTXK β on electrophysiological characteristics of isolated rabbit atrial myocytes.Standard whole-cell patch clamp technique was used to study the effects of multiple concentrations of BmkTXK β on potassium currents and action potentials.Results:①BmkTXK β produced concentration-dependent prolongation of action potential duration at 20%,50%,and 90% repolarization (APD 20,50,90),without significant effect on RMP,APA,or Vmax(n=9).②At a dose of 1 μmol/L,BmkTXK β decreased I to by 41.4% (n=10,P<0.01) at membrane potential of +50 mV (from 13.63±0.87 pA/pF to 7.98±0.78 pA/pF).It significantly reduced Ito with clear concentration-dependence,with an IC 50 value of 0.95 μmol/L.③BmkTXK β inhibited I K current in a concentration-dependent manner.At the dose of 10 μmol/L,the I K was reduced by 39.3% (from 5.86±0.64 pA/pF to 3.56±0.58 pA/pF) at +70 mV (n=6,P<0.05).IC 50 value was 2.76 μmol/L.④But BmkTXK β did not inhibit I K1 with no change on reversal-potential (n=6,P>0.05).Conclusion:BmkTXK β exerts direct blocking effects on I to and I K involved in cardiac repolarization,and has a strong effect on prolonging action potential duration.
基金
湖北省自然科学基金 (批号 :SJ-9710 73)
