甲基莲心碱对心肌细胞I_(Na)、I_(Ca-L)及稳态外向K^+电流的影响

Effects of neferine on I Na , I Ca L and steady state outward K + current of ventricular myocytes

目的 为证明甲基莲心碱（ Ｎｅｆｅｒｉｎｅ， Ｎｅｆ） 对单个心肌细胞离子通道电流的影响及抗心律失常作用的离子通道机制。方法 采用全细胞记录膜片钳技术，记录了 Ｎｅｆ 对培养大鼠心室肌细胞钠电流（ Ｉ Ｎａ） 及豚鼠心室肌细胞动作电位、 Ｉ Ｎａ 、 Ｌ 型钙电流（ Ｉ Ｃａ Ｌ） 及稳态外向 Ｋ＋ 电流的影响。结果 Ｎｅｆ ３０ ，１００ μｍｏｌ· Ｌ－ １ 明显抑制培养大鼠心室肌细胞 Ｉ Ｎａ ，分别从对照水平的（３４ ±０７） ｎ Ａ 降至（２１ ±０５） 和（０４ ±０２） ｎ Ａ。 Ｎｅｆ １０ μｍｏｌ· Ｌ－ １ 可降低豚鼠心室肌细胞动作电位振幅、静息电位，延长动作电位时程。 Ｎｅｆ １０ ，３０ μｍｏｌ· Ｌ－ １ 分别使豚鼠心室肌细胞 Ｉ Ｎａ 及 Ｉ Ｃａ Ｌ从给药前的（７９ ±２１） ｎ Ａ 和（６８９ ±２４３） ｐ Ａ 降至（４０ ±１４） 、（１３ ±０６） ｎ Ａ和（３７４ ±１７２） 、（１０９ ±６７） ｐ Ａ。 Ｎｅｆ １０ μｍｏｌ· Ｌ－ １ 还抑制 Ｉ Ｎａ 、稳态外向 Ｋ＋ 电流和 Ｉ Ｃａ Ｌ的 Ｉ Ｖ 曲线并使后者的峰值电流电位略右移。结论 Ｎｅｆ 有钠、 Ｌ 型钙通道阻滞作用并抑制稳态外向 Ｋ＋ 电流。

AIM To evaluate the effects of neferine (Nef) on the action potentials, sodium current ( I Na ), L type calcium current ( I Ca L ) and steady state outward K + current of the ventricular myocardial cells. METHODS The whole cell recording patch clamp technique was used in cultured rat cardiac cells and isolated guinea pig ventricular myocytes. RESULTS Nef 30,100 μmol·L -1 could inhibit the I Na of cultured rat cardiac cells from (3 4±0 7) nA as control to (2 1±0 5) and (0 4±0 2) nA respectively. Nef 10 μmol·L -1 could obviously reduce the resting potentials, action potential amplitude and prolong the action potential duration of guinea pig ventricular myocytes. Nef 10, 30 μmol·L -1 decreased I Na and I Ca L respectively from (7 9±2 1) nA and (689±243) pA as control level to (4 0±1 4), (1 3±0 6) nA and (374±172)、(109±67) pA. Nef 10 μmol·L -1 could also inhibit the I V curves of I Na , Steady state outward K + current and I Ca L and slightly shift the maximal current potential of the latter to the right. CONCLUSION Nef has blocking actions on sodium and calcium channel and inhibit steady state outward K + currents, which may explain the mechanism of extensive antiarrhythmic actions of Nef.