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肾上腺髓质素对豚鼠心室肌细胞L-型钙通道的调制

杜以梅, 唐明, 刘长金, 骆红艳, 胡新武

华中科技大学同济医学院生理系.湖北,武汉 430030

摘要

应用全细胞膜片钳技术研究了肾上腺髓质素(ADM)对豚鼠心室肌细胞L-型钙电流(I_(Ca,L))的影响及其信号传导机制。结果发现:ADM(1-100nmol/L)浓度依赖性抑制I_(Ca,L)(P<0.05),并可被ADM特异受体阻断剂ADM_(22-52)(100nmol/L)完全阻断。用蛋白激酶A特异拮抗剂H-89(10#mu#mol/L)预处理,对ADM抑制I_(Ca,L)的作用无影响。但用蛋白激酶C(PKC)特异性拮抗剂PKC_(19-36)预处理,可完全阻断ADM的抑制效应;而PKC特异性激动剂PMA则可以模仿ADM的抑制效应(P<0.05)。上述结果提示:ADM作用于特异性ADM受体可浓度依赖性地抑制豚鼠心室肌细胞I_(Ca,L),而此作用可能是PKC介导的。

关键词： 肾上腺髓质素; 心室肌细胞; 受体; 蛋白激酶C; L-型钙通道; 膜片钳技术

Inhibitory effect of adrenomedullin on L-type calcium currents in guinea-pig ventricular myocytes

Du Yimei, Tang Ming, Liu Changjin, Luo Hongyan, Hu Xinwu

Department of Physiology,Tongji Medical College of Huazhong University of Science and Technology.Wuhan 430030,Hubei

Abstract

The effects of adrenomedullin (ADM) on the L-tpe calcium currents (I_(Ca,L)) and the mechanism of the signal transduction process were studied. Enzymatically isolated guinea-pig ventricular myocytes were used to measure I_(Ca,L) with whole-cell patch-clamp techniques. ADM at the concentrations of 1-100 nmol/L decreased I_(Ca,L) in a dose-dependent manner (P<0.05). ADM_(22-52) (100 nmol/L), a specific ADM-receptor antagnoist, completely abolished the ADM-induced inhibition of I_(Ca,L). Pretreatment of the cells with H-89 (10 #mu#mol/L), a specific PKA inhibitor, did not attenuate the effects of ADM. Intracellular application of 10 #mu#mol/L PKC_(19-36), a specific PKC inhibitor, prevented the ADM-induced inhibition of the I_(Ca,L), while the specific PKC activator PMA could mimic the effects of ADM on the the I_(Ca,L). PMA (1 #mu#mol/L) decreased the I_(Ca,L) by 32.26+-4.20% (P<0.05). These findings indicate that ADM can inhibit the I_(Ca,L) in guinea-pig ventricular myocytes, and the inhibition is mediated by the specific ADM-receptor and an activation of protein kinase C.

Key words: Adrenomedullin;Ventricular myocyte;Receptor;Protein kinase C;L-type calcium channel;Patch clamp technique

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引用本文：

杜以梅, 唐明, 刘长金, 骆红艳, 胡新武. 肾上腺髓质素对豚鼠心室肌细胞L-型钙通道的调制[J]. 生理学报 2002; 54 (6): .

Du Yimei, Tang Ming, Liu Changjin, Luo Hongyan, Hu Xinwu. Inhibitory effect of adrenomedullin on L-type calcium currents in guinea-pig ventricular myocytes. Acta Physiol Sin 2002; 54 (6): (in Chinese with English abstract).