Conventional protein kinase C isoforms and cross-activation of protein kinase A regulate cardiac Na+ current

We tested the hypothesis that specific isoforms of protein kinase C (PKC) are responsible for modulation of Na+ current (I-Na) derived from the human cardiac Na+ channel using activators and inhibitors selective for specific PKCs. Experimental results demonstrated that I-Na, suppression was mediated he activation of conventional PKCs (cPKCs) and possibly resulted from channel internalization. In the presence of cPKC inhibition. phorbol ester application unexpectedly increased Na+ current. an effect eliminated he inhibition of protein kinase A. These findings demonstrate complex modulation of cardiac I-Na hi protein kinases and provide further evidence that PKC isoforms have distinct protein targets, (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.