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 by 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 by inhibition of protein kinase A. These findings demonstrate complex modulation of cardiac I(Na) by protein kinases and provide further evidence that PKC isoforms have distinct protein targets.