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-a 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. (C) 1998 Academic Press.