Isoenzyme-specific regulation of cardiac Kv1.5/Kvβ1.2 ion channel complex by protein kinase C: Central role of PKCβII

Fathima Fischer, Nadine Vonderlin, Claudia Seyler, Edgar Zitron, Sevil Korkmaz, Gábor Szabó, Dierk Thomas, Hugo A. Katus, Eberhard P. Scholz

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The ultrarapidly activating delayed rectifier current, I Kur, is a main determinant of atrial repolarization in humans. I Kur and the underlying ion channel complex Kv1.5/Kvβ1.2 are negatively regulated by protein kinase C. However, the exact mode of action is only incompletely understood. We therefore analyzed isoenzyme-specific regulation of the Kv1.5/Kvβ1.2 ion channel complex by PKC. Cloned ion channel subunits were heterologously expressed in Xenopus oocytes, and measurements were performed using the double-electrode voltage-clamp technique. Activation of PKC with phorbol 12-myristate 13-acetate (PMA) resulted in a strong reduction of Kv1.5/Kvβ1.2 current. This effect could be prevented using the PKC inhibitor staurosporine. Using the bisindolylmaleimide Ro-31-8220 as an inhibitor and ingenol as an activator of the conventional PKC isoforms, we were able to show that the Kv1.5/Kvβ1.2 ion channel complex is mainly regulated by conventional isoforms. Whereas pharmacological inhibition of PKCα with HBDDE did not attenuate the PMA-induced effect, current reduction could be prevented using inhibitors of PKCβ. Here, we show the isoform βII plays a central role in the PKC-dependent regulation of Kv1.5/Kvβ1.2 channels. These results add to the current understanding of isoenzyme-selective regulation of cardiac ion channels by protein kinases.

Original languageEnglish
Pages (from-to)469-476
Number of pages8
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume387
Issue number5
DOIs
Publication statusPublished - May 2014

Keywords

  • Adrenergic regulation
  • Isoenzymes
  • Kv1.5
  • Protein kinase C
  • Repolarization
  • Ultrarapid delayed rectifier current

ASJC Scopus subject areas

  • Pharmacology

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