Insulin stimulates the L-type Ca2+ current in rat cardiac myocytes

Objective: The aim was to study the L-type calcium current (I-Ca,I-L) in ca rdiac myocytes as a possible target of insulin in the regulation of cardiac function. Method: Using the whole-cell configuration of the patch-clamp te chnique, we investigated the stimulation of I-Ca,I-L by insulin in isolated rat ventricular myocytes. Results: The stimulation of I-Ca,I-L by insulin was dose-dependent (EC50 = 33 nM) and reversible. Maximum stimulation of I- Ca,I-L over basal I-Ca,I-L was 86 +/- 11 % (n = 25) at 1 mu M insulin Insul in (1 mu M) shifted the current-voltage relationship and potential-dependen t availability of I-Ca,I-L to more negative potentials by about 3.5 and 1.5 mV, respectively. The maximum conductance of I-Ca,I-L was increased by 1 m u M insulin, from 26+/-4 to 39+/-5 nS (n = 11). Isoproterenol (100 nM), whi ch stimulated I-Ca,I-L by 156+/-23% (n = 10) over basal I-Ca,I-L, acted fas ter than insulin. The half-maximum stimulation of I-Ca,I-L by isoproterenol and insulin was reached after 44+/-5 and 80+/-9 s, respectively. Insulin a nd isoproterenol responses were not additive. Insulin (1 gamma M) and isopr oterenol(100 nM) stimulation of I-Ca,I-L was inhibited by Rp-cAMPS (1 mM) t o 12+/-3 and 32+/-4%, respectively. Insulin (1 mu M) increased cAMP content in rat cardiomyocytes by about two-fold. Insulin-like growth factor-1 (IGF -1; 5 mu M) increased I-Ca,I-L by only 5.9+/-0.9% (n=6). Conclusions: Our d ata show that insulin stimulates the L-type calcium current in isolated rat ventricular myocytes in a dose-dependent and reversible manner and suggest that this effect is mediated by insulin receptors and the cAMP-dependent p rotein kinase. (C) 1999 Elsevier Science B.V. All rights reserved.