Calcitonin gene-related peptide suppresses the transient outward current in rat ventricular myocytes

The effects of calcitonin gene-related peptide (CGRP) on the transient outw ard current (I-to) and the L-type calcium current (I-Ca,I-L) were investiga ted in isolated rat ventricular cardiomyocytes using the whole-cell, patch- clamp technique. CORP influenced neither the amplitude nor the time course of I-Ca,I-L On the other hand, at all membrane potentials at which a signif icant I-to was elicited, CGRP decreased its amplitude. The effect on I-to w as completely reversible and independent of membrane potential. The steady- state activation and inactivation curves of I-to were not influenced by CGR P. The time course of I-to inactivation was satisfactorily fitted by two ex ponentials. Both the fast and the slow time constants of inactivation were voltage independent and were not influenced by CGRP. The effect of CGRP on I-to was concentration dependent with half-maximum inhibition at 99 nM. Che lerythrine, a selective inhibitor of protein kinase C, prevented the effect of CORP on I-to. The data indicate that CORP suppresses I-to in a concentr ation-dependent, but membrane potential-independent manner and that the eff ect is probably mediated via a protein kinase C-dependent pathway.