Enhancement of rabbit cardiac sodium channels by β-adrenergic stimulation

J. J. Matsuda, H. Lee, E. F. Shibata

Research output: Contribution to journalArticle

129 Scopus citations

Abstract

Voltage-dependent sodium channels from a variety of tissues are known to be phosphorylated by the cAMP-dependent protein kinase, protein kinase A. However, the functional significance of sodium channel phosphorylation is not clearly understood. Using whole-cell voltage-clamp techniques, we show that sodium currents (I(Na)s) in rabbit cardiac myocytes are enhanced by isoproterenol (ISO). This enhancement of I(Na) by ISO 1) is holding potential dependent, 2) can be mimicked by forskolin and dibutyryl cAMP, and 3) is accompanied by an increase in the rate of Na+ channel inactivation. In single-channel, inside-out patch experiments, the catalytic subunit of protein kinase A also enhances I(Na) and increases the rate of inactivation, suggesting that cardiac Na+ channel phosphorylation may be physiologically important. Addition of the protein kinase A inhibitor to the pipette solution in whole-cell experiments blocks the stimulatory effect of forskolin without blocking the effect of ISO, suggesting that ISO also enhances I(Na) through a cAMP-independent pathway. To determine if ISO may stimulate I(Na) through a direct G protein pathway, single channels were recorded in the presence of the G(s)-activating GTP analogue, GTPγS, and the stimulatory G protein subunit, G(sα). Both of these agents enhanced I(Na) without affecting the rate of Na+ channel inactivation. These results suggest that ISO enhances rabbit cardiac I(Na) through a dual (direct and indirect) G protein regulatory pathway.

Original languageEnglish (US)
Pages (from-to)199-207
Number of pages9
JournalCirculation research
Volume70
Issue number1
DOIs
StatePublished - Jan 1 1992

Keywords

  • isoproterenol
  • protein kinase A
  • sodium channels
  • β-adrenergic stimulation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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