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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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Citing This Article：

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).