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目的:探讨阿魏酸钠对家兔心室肌细胞膜延迟整流钾电流快速与缓慢激活成分(IKr、IKs)、内向整流钾电流(IK1)、瞬时外向钾电流(Ito)的影响。方法:酶解法分离单个家兔心室肌细胞,以经典的Ⅲ类药胺碘酮为对照,采用全细胞膜片钳技术记录浓度为3.0、10.0、30.0、100.0μmol/L的阿魏酸钠对IKr、IKs、IK1、Ito的作用。结果:阿魏酸钠的作用弱于胺碘酮,二者均可浓度依赖性抑制IKr、IKs时间依赖性外向电流及尾电流(IKr,tail、IKs,tail)。不同浓度的阿魏酸钠对IKr,tail的抑制率为:(12.1±2.5)%、(24.1±3.0)%、(47.0±5.8)%及(58.5±8.3)%(n=5,P<0.05);对IKs,tail的抑制率为:(15.6±6.4)%、(27.1±6.5)%、(45.6±5.8)%及(51.8±6.6)%(n=5,P<0.05),其对IKr,tail及IKs,tail的半数抑制浓度(IC50)均大于胺碘酮(43.6∶3.48μmol/L,44.9∶5.11μmol/L)。30.0、100.0μmol/L阿魏酸钠及10.0、30.0μmol/L胺碘酮可使IK1的I-V曲线左移,在-100mV及-20mV测试电压下,阿魏酸钠对IK1内向、外向电流抑制率小于胺碘酮(n=5,P<0.05)。阿魏酸钠与胺碘酮均不影响Ito及其I-V曲线。结论:阿魏酸钠复合阻滞复极期多种钾电流,可能是其抗心律失常作用的电生理机制之一。
OBJECTIVE: To investigate the effects of sodium ferulate on delayed rectifier potassium currents in rabbit ventricular myocytes and the effects of slow activation (IKr, IKs), inward rectifier potassium current (IK1), and transient outward potassium current (Ito). METHODS: Single rabbit ventricular myocytes were isolated by enzymatic hydrolysis. The classic class III drug amiodarone was used as control. Whole-cell patch clamp technique was used to record the concentrations of sodium ferulate at 3.0, 10.0, 30.0 and 100.0 μmol/L for IKr. The role of IKs, IK1, Ito. Results: The effect of sodium ferulate was weaker than that of amiodarone. Both of them could inhibit the time-dependent outward currents and tail currents (IKr, tail, IKs, tail) of IKr and IKs in a concentration-dependent manner. Different concentrations of sodium ferulate inhibited IKr and tail by (12.1±2.5)%, (24.1±3.0)%, (47.0±5.8)%, and (58.5±8.3)% (n=5, P< 0.05); The inhibition rates of IKs and tails were: (15.6±6.4)%, (27.1±6.5)%, (45.6±5.8)%, and (51.8±6.6)% (n=5, P<0.05). The IC50 of IKr, tail, IKs and tail were higher than those of amiodarone (43.6:3.48 μmol/L, 44.9:5.11 μmol/L). 30.0, 100.0 μmol/L sodium ferulate and 10.0, 30.0 μmol/L amiodarone left the IV curve of IK1 to the left, and sodium ferulate inhibited the inward and outward currents of IK1 at -100 mV and -20 mV test voltage. The rate was less than amiodarone (n=5, P<0.05). Both sodium ferulate and amiodarone did not affect Ito and its I-V curve. CONCLUSION: Sodium ferulate compound block multiple potassium currents during repolarization may be one of the electrophysiological mechanisms of antiarrhythmic effects.