大蒜素对心室肌细胞膜钠通道电流的影响

Effect of garlicin on sodium channel current in rat ventricular myocytes

目的:研究大蒜素对心室肌细胞膜钠通道电流(I_(Na))的影响,探讨大蒜素在离子通道水平的药理作用机制。方法:用急性酶解法分离大鼠心室肌细胞,应用膜片钳全细胞记录技术,观察不同浓度的大蒜素对钠通道的影响。结果:(1)快钠通道电流:大蒜素对豚鼠心室肌细胞I_(Na)呈电压依赖性和浓度依赖的抑制作用。(2)大蒜素对I_(Na)电流密度-电压关系(I-V)曲线的影响:给药前I_(Na)电流密度在膜电位-40mV达到最大峰值为(-13.41±6.95)pA/pF;在500μmol/L灌流法给药后,电流密度最大峰值为(-8.53±3.70)pA/pF,给药后电流密度减少约48%。给药前后电流密度变化有显著差异(P<0.01)。(3)大蒜素对I_(Na)激活-失活曲线的影响:在大蒜素500μmol/L灌流法给药后,激活曲线显示给药前后半数激活电压为(-44.72±15.61)mV vs(-45.66±17.86)mV,斜率因子为-2.7±0.8vs-2.2±0.7,给药前后变化无显著差异。失活曲线显示大蒜素使失活曲线向负电位方向变化,差异显著;半数失活电压为(-88.61±9.60)mV vs(-103.03±8.90)mV(P<0.01),斜率因子为-7.85±0.88vs -7.55±2.75(P>0.05)。结论:大蒜素可浓度依赖性和电压依赖性地抑制心肌细胞膜钠通道电流;给药后I-V曲线上移,显著减少电流密度;其对失活曲线有明显影响,提示大蒜素主要作用于钠通道的失活态。

AIM：To observe the effect of garlicin on sodium channel（I_（Na））in isolated ventricular myocytes of rats.METHODS：The ventricular myocytes of rats were obtained by enzymatic dissociation and treated with different concentrations of garlicin.The change of I_（Na）was recorded by the technique of whole-cell patch clamp recording.RESULTS： Garlicin decreased the I_（Na）of isolated ventricular myocytes in a dose-and voltage-dependent manner.The current density was elevated to peak[（-13.41±6.95）pA/pF]under the condition that the membrane voltage was-40 mV before treated with garlicin.The current density was decreased by 48%from peak after treated with 500μmol/L garlicin[（-8.53±3.70）pA/pF,P〈0.01].No significant change of the active curve with the use of garlicin was observed.The median inactive voltages of the inactive curves before and after garlicin treatment were（-88.61±9.60）mV and（-103.03±8.90）mV（P〈0.01）,respectively,and the slopes were-7.85±0.88 and-7.55±2.75（P〉0.05）,respectively, indicating that garlicin made a shift to the negative direction.CONCLUSION：Garlicin treatment induced the current density -voltage curve of I_（Na）to shift up and significantly decreased the current density.The inactive curve of sodium channel moved to the left,while the current density was not decreased after treated with garlicin.Garlicin blocks sodium channel in its inactive state in a dose-and voltage-dependent manner.