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(英文)  

Carbachol augments Na/Caexchange currentvia M_2 muscarinic receptors in guinea pig ventricular myocytes

作　　者：崔香丽[1] 陈还珍[1] 武冬梅[1] 吴博威[1] 

机构地区：[1]山西医科大学生理教研室,太原030001

出　　处：《生理学报》2004年第6期713-716,共4页Acta Physiologica Sinica

基　　金：This work was supported by the Natural Science Foundation of Shanxi Province (No 20031101).

摘　　要：本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(ICa)和钠钙交换电流(INa/Ca)的效应。结果表明, CCh(100 μmol/L)分别使正向INa/Ca从对照组的(1.2 ± 0.1) pA/pF 增加到(2.0 ± 0.3) pA/pF,使反向 INa/Ca 从对照组的(1.3 ± 0.5) pA/pF 增加到(2.1 ± 0.8) pA/pF (P<0.01)。CCh对ICa无影响。CCh 对INa/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 M2 毒蕈碱受体所介导的。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 (ICa) and Na/Ca exchange current (INa/Ca) were observed in voltage-clamped guinea pig ventricular myocytes by using Axon 200A amplifier. The results showed that CCh (100 μmol/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 ICa. The stimulating effect of CCh on INa/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 M2 muscarinic receptors. It completely abolished INa/Ca induced by 100 μmol/L CCh, indicating that the effect of CCh on INa/Ca was mediated by M2 muscarinic receptors. It is generally accepted that contraction in cardiac myocytes results from elevation of intracellular Ca2+ concentration. Ca2+ enters the cells through two pathways: L-type Ca2+ 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 Ca2+ 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 M2 muscarinic receptors.

关 键 词：氨甲酰胆碱 毒蕈碱受体 钠钙交换 methoctramine 豚鼠 心肌细胞 

分 类 号：Q421[生物学—神经生物学]