Insulin stimulates the L-type Ca2+ current in rat cardiac myocytes.
OBJECTIVE
The aim was to study the L-type calcium current (ICa,L) in cardiac myocytes as a possible target of insulin in the regulation of cardiac function.


METHODS
Using the whole-cell configuration of the patch-clamp technique, we investigated the stimulation of ICa,L by insulin in isolated rat ventricular myocytes.


RESULTS
The stimulation of ICa,L by insulin was dose-dependent (EC50 = 33 nM) and reversible. Maximum stimulation of ICa,L over basal ICa,L was 86 +/- 11% (n = 25) at 1 microM insulin. Insulin (1 microM) shifted the current-voltage relationship and potential-dependent availability of ICa,L to more negative potentials by about 3.5 and 1.5 mV, respectively. The maximum conductance of ICa,L was increased by 1 microM insulin, from 26 +/- 4 to 39 +/- 5 nS (n = 11). Isoproterenol (100 nM), which stimulated ICa,L by 156 +/- 23% (n = 10) over basal ICa,L, acted faster than insulin. The half-maximum stimulation of ICa,L by isoproterenol and insulin was reached after 44 +/- 5 and 80 +/- 9 s, respectively. Insulin and isoproterenol responses were not additive. Insulin (1 microM) and isoproterenol (100 nM) stimulation of ICa,L was inhibited by Rp-cAMPS (1 mM) to 12 +/- 3 and 32 +/- 4%, respectively. Insulin (1 microM) increased cAMP content in rat cardiomyocytes by about two-fold. Insulin-like growth factor-1 (IGF-1; 5 microM) increased ICa,L by only 5.9 +/- 0.9% (n = 6).


CONCLUSIONS
Our data 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 protein kinase.
Aulbach
F
F
Medical University Clinic, Institute of Clinical Biochemistry and Pathobiochemistry, Würzburg, Germany.
Simm
A
A
Maier
S
S
Langenfeld
H
H
Walter
U
U
Kersting
U
U
Kirstein
M
M
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000252:Calcium-Transporting ATPases / Q000187:drug effects*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D013268:Stimulation, Chemical; D013873:Thionucleotides / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D004791:Enzyme Inhibitors; D007328:Insulin; D013873:Thionucleotides; C016957:adenosine-3',5'-cyclic phosphorothioate; D007334:Insulin-Like Growth Factor I; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000252:Calcium-Transporting ATPases; D007545:Isoproterenol