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.
Shin
H G
HG
Department of Pharmacology, Vanderbilt University School of Medicine, Room 559 Preston Research Building, 23rd and Pierce Avenues, Nashville, TN 37232-6602, USA.
Murray
K T
KT
D000818:Animals; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004553:Electric Conductivity; D004789:Enzyme Activation; D006801:Humans; D007527:Isoenzymes / Q000502:physiology; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D064546:Protein Kinase C beta; D051744:Protein Kinase C-epsilon; D015222:Sodium Channels / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014981:Xenopus
D007527:Isoenzymes; D020033:Protein Isoforms; D015222:Sodium Channels; D003208:Concanavalin A; D017868:Cyclic AMP-Dependent Protein Kinases; C497255:PRKCE protein, human; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D051744:Protein Kinase C-epsilon; D013755:Tetradecanoylphorbol Acetate