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

FEBS Letters

Shin, Hyeon-Gyu¹  Murray, Katherine T¹ 

[1] Departments of Pharmacology and Medicine, Vanderbilt University School of Medicine, Room 559 Preston Research Building, 23rd and Pierce Avenues, Nashville, TN 37232-6602, USA

关键词: Sodium channel;    Cardiac;    Protein kinase C;    Protein kinase A;    Trafficking;    Xenopus oocyte;    PKC;    protein kinase C;    cPKC;    conventional PKC;    nPKC;    novel PKC;    aPKC;    atypical PKC;    PMA;    phorbol 12-myristate 13-acetate;    Tx;    thymeleatoxin;    Bis I;    bisindolemaleamide I;    IDB;    ingenol 3;    20-dibenzoate;    PKA;    protein kinase A;    PKI;    protein kinase A inhibitor 5-24;    ConA;    concanavalin A;   

DOI  :  10.1016/S0014-5793(01)02380-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown