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Isolation of High Quality Murine Atrial and Ventricular Myocytes for Simultaneous Measurements of Ca2+ Transients and L-Type Calcium Current
06:22

Isolation of High Quality Murine Atrial and Ventricular Myocytes for Simultaneous Measurements of Ca2+ Transients and L-Type Calcium Current

Published on: November 3, 2020

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

Atsuko Yatani1, Keiichi Irie, Takayuki Otani

  • 1Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, USA.

American Journal of Physiology. Heart and Circulatory Physiology
|October 9, 2004
PubMed

Insights

Rho GDP dissociation inhibitor alpha (Rho GDI-alpha) regulates cardiac L-type Ca2+ channels. Overexpression decreases channel activity, implicating RhoA signaling in cardiac function control.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Cell Physiology

Background:

  • Ionic channel regulation is crucial for cardiac function.
  • Rho family small G proteins are implicated in cellular signaling pathways.

Purpose of the Study:

  • To investigate the role of Rho GDP dissociation inhibitor alpha (Rho GDI-alpha) in regulating L-type Ca2+ currents in ventricular cardiomyocytes.
  • To determine the specific Rho family members involved in this regulation.

Main Methods:

  • Utilized transgenic mice overexpressing Rho GDI-alpha.
  • Performed electrophysiological recordings (L-type Ca2+ currents, K+ currents) on isolated ventricular myocytes.
  • Assessed mRNA and protein levels of Ca2+ channel alpha1-subunits.
  • Employed TAT-mediated protein transduction to deliver Rho GDI-alpha and dominant-negative RhoA, Rac-1, or Cdc42 into myocytes.

Main Results:

  • Overexpression of Rho GDI-alpha in ventricular myocytes significantly reduced L-type Ca2+ current density (~40%).
  • Ca2+ channel activity, not expression levels, was altered; agonists increased currents similarly in transgenic and nontransgenic myocytes.
  • Inward rectifier and transient outward K+ currents, as well as basal twitch and Ca2+ transient properties, remained unchanged.
  • Direct protein delivery of Rho GDI-alpha mimicked the effect, confirming a primary role.
  • Dominant-negative RhoA, but not Rac-1 or Cdc42, inhibited Ca2+ current density, indicating RhoA mediation.

Conclusions:

  • Rho GDI-alpha negatively regulates L-type Ca2+ channel activity in ventricular cardiomyocytes.
  • This regulation is mediated by the RhoA signaling pathway.
  • L-type Ca2+ channel activity represents a novel downstream target of RhoA signaling in the heart.

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