The effects of calcitonin gene-related peptide (CGRP) on the transient outward current (Ito) and the L-type calcium current (ICa,L) were investigated in isolated rat ventricular cardiomyocytes using the whole-cell, patch-clamp technique. CGRP influenced neither the amplitude nor the time course of ICa,L. On the other hand, at all membrane potentials at which a significant Ito was elicited, CGRP decreased its amplitude. The effect on Ito was completely reversible and independent of membrane potential. The steady-state activation and inactivation curves of Ito were not influenced by CGRP. The time course of Ito inactivation was satisfactorily fitted by two exponentials. Both the fast and the slow time constants of inactivation were voltage independent and were not influenced by CGRP. The effect of CGRP on Ito was concentration dependent with half-maximum inhibition at 99 nM. Chelerythrine, a selective inhibitor of protein kinase C, prevented the effect of CGRP on Ito. The data indicate that CGRP suppresses Ito in a concentration-dependent, but membrane potential-independent manner and that the effect is probably mediated via a protein kinase C-dependent pathway.

Department of Physiology Faculty of Medicine Charles University Pilsen Czech Republic

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