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

Objective: The L-type calcium current (I ) in isolated human atrial myocytes was investigated as a possible target of insulin in the Ca,L regulation of cardiac function. Methods: Atrial myocytes were obtained from patients undergoing cardiac surgery. Using the whole-cell configuration of the patch-clamp technique, we investigated the stimulation of I by insulin in single human atrial myocytes. Results: Ca,L We found a dose-dependent stimulation of I by insulin at concentrations of 100 nM, 1 mM and 10 mM. Maximum stimulation of I Ca,L Ca,L over basal I was 140612% (n511) at 10 mM insulin. The maximum conductance of I was increased by 10 mM insulin from Ca,L Ca,L 4.060.3 nS to 8.361.0 nS (n56). The stimulation of I by insulin was dose-dependent and reversible. Isoproterenol (10 nM) that Ca,L stimulates I by 271648% (n510) over basal I acted faster than insulin. The half-maximum stimulation of I by isoproterenol Ca,L Ca,L Ca,L and insulin (10 mM) was reached after 3162 s and 5265 s, respectively. The insulin effect shown was totally reversed by acetylcholine (3 mM) which is known to inhibit adenylyl cyclase activity /cAMP-production via G -proteins. Also, the selective insulin receptor tyrosine i kinase inhibitor (hydroxy-2-naphthanelyl-methyl)phosphonic acid completely inhibited the insulin induced effect. Conclusion: Our data show that insulin stimulates the L-type calcium current in isolated human atrial myocytes in a dose-dependent and reversible manner which appears to involve the insulin receptor tyrosine kinase. Insulin regulation of I in human atrial myocytes may be an interesting Ca,L system for the analysis of the metabolic syndrome in man.  1999 Elsevier Science B.V. All rights reserved.