Stimulation of L-type Ca2+ current in human atrial myocytes by insulin

Objective: The L-type calcium current (I-Ca,I-L) in isolated human atrial m yocytes was investigated as a possible target of insulin in the regulation of cardiac function. Methods: Atrial myocytes were obtained from patients u ndergoing cardiac surgery. Using the whole-cell configuration of the patch- clamp technique, we investigated the stimulation of I-Ca,I-L by insulin in single human atrial myocytes. Results: We found a dose-dependent stimulatio n of I-Ca,I-L by insulin at concentrations of 100 nM, 1 mu M and 10 mu M. M aximum stimulation of I-Ca,I-L over basal I-Ca,I-L was 140+/-12% (n=11) at 10 mu M insulin. The maximum conductance of I-Ca,I-L was increased by 10 mu M insulin from 4.0+/-0.3 nS to 8.3+/-1.0 nS (n=6). The stimulation of I-Ca ,I-L by insulin was dose-dependent and reversible. Isoproterenol (10 nM) th at stimulates I-Ca,I-L by 271+/-48% (n=10) over basal I-Ca,I-L acted faster than insulin. The half-maximum stimulation of I-Ca,I-L by isoproterenol an d insulin (10 mu M) was reached after 31+/-2 s and 52+/-5 s, respectively. The insulin effect shown was totally reversed by acetylcholine (3 mu M) whi ch is known to inhibit adenylyl cyclase activity/cAMP-production via G(i)-p roteins. Also, the selective insulin receptor tyrosine kinase inhibitor (hy droxy-2-naphthanelyl-methyl)phosphonic acid completely inhibited the insuli n induced effect. Conclusion: Our data show that insulin stimulates the L-t ype calcium current in isolated human atrial myocytes in a dose-dependent a nd reversible manner which appears to involve the insulin receptor tyrosine kinase. Insulin regulation of I-Ca,I-L in human atrial myocytes may be an interesting system for the analysis of the metabolic syndrome in man. (C) 1 999 Elsevier Science B.V. All rights reserved.