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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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Inhibition of Rac1 reduces store overload-induced calcium release and protects against ventricular arrhythmia

Lili Zhang1,2, Xiangru Lu2, Le Gui2,3

  • 1Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Journal of Cellular and Molecular Medicine
|May 26, 2016
PubMed

Insights

Rac1 activation contributes to cardiac arrhythmia during myocardial ischemia and reperfusion (I/R). Inhibiting Rac1 reduces arrhythmia and protects the heart by suppressing store overload-induced Ca2+ release (SOICR).

Area of Science:

  • Cardiovascular Biology
  • Molecular Cardiology
  • Cellular Signaling

Background:

  • Rac1, a small GTPase, is involved in cellular processes like reactive oxygen species (ROS) production.
  • The role of Rac1 activation in myocardial ischemia and reperfusion (I/R)-induced cardiac arrhythmia remains unclear.

Purpose of the Study:

  • To investigate the impact of Rac1 inhibition on store overload-induced Ca2+ release (SOICR) and ventricular arrhythmia during myocardial I/R.
  • To explore Rac1's contribution to arrhythmogenesis in the context of I/R injury.

Main Methods:

  • Utilized adult Rac1(f/f) and cardiac-specific Rac1 knockdown (Rac1(ckd)) mice subjected to myocardial I/R.
  • Monitored ventricular arrhythmia via electrocardiograms (ECGs) and performed Ca2+ imaging in cardiomyocytes.
  • Assessed Rac1 activity, ROS production, and ryanodine receptor 2 (RyR2) oxidation.

Main Results:

  • Myocardial Rac1 activity and ventricular arrhythmia increased during I/R in wild-type mice.
  • Rac1 inhibition (genetic or pharmacological with NSC23766) significantly reduced I/R-induced ventricular arrhythmia.
  • Rac1 inhibition diminished SOICR in cardiomyocytes and decreased I/R-induced ROS production and RyR2 oxidation.

Conclusions:

  • Rac1 activation promotes ventricular arrhythmia during myocardial I/R.
  • Inhibition of Rac1 suppresses SOICR and offers protection against ventricular arrhythmia.
  • Blocking Rac1 activation presents a potential therapeutic strategy for cardiac arrhythmias in ischemic heart disease.
Keywords:
Rac1arrhythmiaischaemia and reperfusionreactive oxygen speciesstore overload-induced calcium release

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