Modulation of cardiac Ca2+ channels by IGF1.
Although there are several reports on the regulation of neuronal and skeletal muscle voltage-sensitive calcium channels by IGF1, the effects of short-term IGF1 exposure on cardiac Ca2+ channels have not been described. We measured the activity of nitrendipine-sensitive Ca2+ channels of intact cardiac myocytes in the presence of IGF1 by monitoring unidirectional Mn2+ influx measured as the quench of cytosolic fura-2 in electrically stimulated or K+-depolarized cells. Maximal channel activation was observed after 10 min of preincubation with IGF1, which gave an increase of 216 +/- 25%. Treatment with the protein kinase C inhibitors bisindolylmaleimide I and chelerythrine mimicked the augmentation effect of IGF1, whereas PMA blocked enhancement of Mn2+ influx by IGF1. These results demonstrate that acute IGF1 augments dihydropyridine-sensitive sarcolemmal Ca2+ channel activity and that protein kinase C may contribute to the regulation of cardiac Ca2+ channels by IGF1.
Solem
M L
ML
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, 1020 Locust Street, Philadelphia, Pennsylvania, 19107, USA. solem1@jeflin.tju.edu
Thomas
A P
AP
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002227:Carbazoles / Q000494:pharmacology; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006321:Heart / Q000502:physiology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology* / Q000502:physiology; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008345:Manganese / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D012508:Sarcolemma / Q000378:metabolism; D013449:Sulfonamides; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D015220:Calcium Channels; D002227:Carbazoles; D002867:Chromones; D004791:Enzyme Inhibitors; D007211:Indoles; D007546:Isoquinolines; D009025:Morpholines; D011994:Recombinant Proteins; D013449:Sulfonamides; C081021:Go 6976; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D008345:Manganese; D007334:Insulin-Like Growth Factor I; D011493:Protein Kinase C; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium