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Isolation of Human Atrial Myocytes for Simultaneous Measurements of Ca2+ Transients and Membrane Currents
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Isolation of Human Atrial Myocytes for Simultaneous Measurements of Ca2+ Transients and Membrane Currents

Published on: July 3, 2013

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Absence of the Regulator of G-protein Signaling, RGS4, Predisposes to Atrial Fibrillation and Is Associated with

Aaisha Opel1, Muriel Nobles2, David Montaigne2

  • 1From the British Heart Foundation Laboratories, Department of Medicine, University College London, Rayne Institute, London WC1E 6JJ, United Kingdom and the William Harvey Heart Centre, Barts & The London School of Medicine & Dentistry, London EC1M 6BQ, United Kingdom.

The Journal of Biological Chemistry
|June 20, 2015
PubMed

Insights

Regulators of G-protein signaling, specifically RGS4, are crucial for preventing atrial fibrillation (AF). Loss of RGS4 function in mice leads to increased AF susceptibility due to abnormal calcium handling in heart cells.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Genetics

Background:

  • The molecular mechanisms underlying atrial fibrillation (AF) predisposition are not fully understood.
  • The role of regulators of G-protein signaling (RGS) in AF pathogenesis remains unclear.

Purpose of the Study:

  • To investigate if reduced RGS4 function promotes AF.
  • To elucidate the mechanism by which RGS4 deficiency may lead to AF.

Main Methods:

  • Utilized a global RGS4 knockout mouse model (RGS4(-/-)) and wild-type littermate controls (RGS4(+/+)).
  • Performed in vivo electrophysiology with atrial burst pacing.
  • Analyzed isolated atrial cells for calcium (Ca2+) dynamics.
  • Studied isolated left atria using a multielectrode array.

Main Results:

  • RGS4(-/-) mice exhibited a higher incidence of AF compared to controls.
  • RGS4 deletion led to increased basal Ca2+ spark frequency and abnormal spontaneous Ca2+ release in atrial cells.
  • Abnormal electrical events were observed in RGS4(-/-) atria after pacing.

Conclusions:

  • RGS4 deficiency predisposes to AF.
  • This predisposition is linked to enhanced Gαq/11-IP3 pathway activity, causing aberrant Ca2+ release and electrical disturbances in the atria.
Keywords:
arrhythmiaatrial fibrillationcalciumcardiac musclecell signalingelectrophysiologyinositol 1,4,5-trisphosphate (IP3)regulator of G protein signaling (RGS)

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