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氨甲酰胆碱通过M_(2)毒蕈碱受体增加豚鼠心肌细胞钠钙交换电流

崔香丽, 陈还珍, 武冬梅, 吴博威

山西医科大学生理教研室.山西,太原 030001

摘要

该文旨在研究氨甲酰胆碱(carbachol,CCh)对豚鼠心肌的正性变力性机制。用Axon200A膜片钳放大器观察CCh对电压钳制下的豚鼠心肌细胞L--型钙电流(I_(Ca))和钠钙交换电流(I_(Na/Ca))的效应。结果表明,CCh(100#mu#mol/L)分别使正向I_(Na/Ca)从对照组的(1.2±0.1)pA/pF增加到(2.0±0.3)pA/pF,使反向I_(Na/Ca)从对照组的(1.3±0.5)pA/pF增加到(2.1±0.8)pA/pF({sl P}＜0.01)。CCh对I_(Ca)无影响。CCh对I_(Na/Ca)的激动作用可被阿托品和methoctramine所阻断。以上结果提示,CCh对豚鼠心脏的正性变力作用是通过激动了钠钙交换,而且是M_(2)毒蕈碱受体所介导的。

关键词： 氨甲酰胆碱; 毒蕈碱受体; 钠钙交换; methoctramine; 豚鼠; 心肌细胞

Carbachol augments Na/Ca exchange current via M_(2) muscarinic receptors in guinea pig ventricular myocytes

Cui Xiangli, Chen Huanzhen, Wu Dongmei, Wu Bowei

Departmentn of Physiology,Shanxi Medical University.Taiyuan 030001,Shanxi

Abstract

Stimulation of cardiac mAChRs by carbachol (CCh) produces a biphasic inotropic response. The mechanisms of the positive inotropic response by higher concentration of CCh appear to be paradoxical. This article was aimed to study the mechanism of the positive inotropic effect of CCh in guinea pig ventricular myocytes. The effects of CCh on L-type calcium current (I_(Ca)) and Na/Ca exchange current (I_(Na/Ca)) were observed in voltage-clamped guinea pig ventricular myocytes by using Axon 200A amplifier. The results showed that CCh (100 #mu#mol/L) increased both forword mode and reverse mode INa/Ca from (1.2±0.1) pA/pF to (2.0±0.3) pA/pF for forward mode (P＜0.01) and from (1.3+0.5) pA/pF to (2.1+0.8) pA/pF for reverse mode (P＜0.01), respectively. CCh had no effect on I_(Ca). The stimulating effect of CCh on I_(Na/Ca) could be blocked by application of atropine, a nonselective blocker of muscarinic receptors,which means that the stimulating effect of CCh is through the activation of muscarinic receptors. We made a further study by using methoctramine, a selective antagonist of M_(2) muscarinic receptors. It completely abolished I_(Na/Ca) induced by 100 #mu#mol/L CCh, indicating that the effect of CCh on I_(Na/Ca) was mediated by M_(2) muscarinic receptors. It is generally accepted that contraction in cardiac myocytes results from elevation of intracellular Ca~(2+) concentration. Ca~(2+) enters the cells through two pathways: L-type Ca~(2+) channels and, less importantly, reverse mode Na/Ca exchange. The calcium influx via both pathways promotes the contraction of cardiac myocytes.Because CCh had no effect on L-type Ca~(2+) current, the increase in Na/Ca exchange current might be the main factor in the positive inotropism of CCh. These results suggest that the positive inotropic effect of CCh in guinea pig heart is through stimulation of Na/Ca exchange and is mediated by M_(2) muscarinic receptors.

Key words: carbachol;muscarinic receptor;Na-Ca exchanger;methoctramine;Guinea pig;cardiomegaly

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引用本文：

崔香丽, 陈还珍, 武冬梅, 吴博威. 氨甲酰胆碱通过M_(2)毒蕈碱受体增加豚鼠心肌细胞钠钙交换电流[J]. 生理学报 2004; 56 (6): .

Cui Xiangli, Chen Huanzhen, Wu Dongmei, Wu Bowei. Carbachol augments Na/Ca exchange current via M_(2) muscarinic receptors in guinea pig ventricular myocytes. Acta Physiol Sin 2004; 56 (6): (in Chinese with English abstract).