RhoA GTPase regulates L-type Ca2+ currents in cardiac myocytes

Atsuko Yatani, Keiichi Irie, Takayuki Otani, Maha Abdellatif, Lei Wei

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Regulation of ionic channels plays a pivotal role in controlling cardiac function. Here we show that the Rho family of small G proteins regulates L-type Ca2+ currents in ventricular cardiomyocytes. Ventricular myocytes isolated from transgenic (TG) mice that overexpress the specific GDP dissociation inhibitor Rho GDI-α exhibited significantly decreased basal L-type Ca2+ current density (∼40%) compared with myocytes from nontransgenic (NTG) mice. The Ca2+ channel agonist BAY K 8644 and the β-adrenergic agonist isoproterenol increased Ca2+ currents in both NTG and TG myocytes to a similar maximal level, and no changes in mRNA or protein levels were observed in the Ca2+ channel α1- subunits. These results suggest that the channel activity but not the expression level was altered in TG myocytes. In addition, the densities of inward rectifier and transient outward K+ currents were unchanged in TG myocytes. The amplitudes and rates of basal twitches and Ca2+ transients were also similar between the two groups. When the protein was delivered directly into adult ventricular myocytes via TAT-mediated protein transduction, Rho GDI-α significantly decreased Ca2+ current density, which supports the idea that the defective Ca2+ channel activity in TG myocytes was a primary effect of the transgene. In addition, expression of a dominant-negative RhoA but not a dominant-negative Rac-1 or Cdc42 also significantly decreased Ca2+ current density, which indicates that inhibition of Ca2+ channel activity by overexpression of Rho GDI-α is mediated by inhibition of RhoA. This study points to the L-type Ca2+ channel activity as a novel downstream target of the RhoA signaling pathway.

Original languageEnglish (US)
Pages (from-to)H650-H659
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume288
Issue number2 57-2
DOIs
StatePublished - Feb 1 2005
Externally publishedYes

Keywords

  • Cardiomyocyte
  • GDP dissociation inhibitor
  • K channel
  • TAT-mediated protein transduction
  • Ventricular

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Fingerprint Dive into the research topics of 'RhoA GTPase regulates L-type Ca<sup>2+</sup> currents in cardiac myocytes'. Together they form a unique fingerprint.

  • Cite this