目的:研究大蒜素对心室肌细胞膜钠通道电流(INa)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INa呈电压依赖性和浓度依赖的抑制作用.(2)大蒜素对INa电流密度-电压关系(I-V)曲线的影响:给药前INa电流密度在膜电位-40 mV达到最大峰值为(-13.41±6.95)pA/pF;在500 μmol/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INa激活-失活曲线的影响:在大蒜素500 μmol/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±0.8 vs -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±0.88 vs -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( INa ) in isolated ventricular myocytes of rats.METHODS : The ventricular myocytes of rats were ohtained by enzymatic dissociation and treated with different concentrations of garlicin.The change of INa was recorded by the technique of whole - cell patch clamp recording.RESULTS :Garlicin decreased the INa 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 500 μmol/L garlicin [ ( - 8.53 ±3.70) pA/pF, P ＜0.01 ] .No significant change of the active curve with the use of garlicin was ohserved.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 INa 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.
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