Gap junction inhibition by heptanol increases ventricular arrhythmogenicity by reducing conduction velocity without

Gary Tse1, Jie Ming Yeo2, Vivian Tse3

  • 1Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, P.R. China.

Molecular Medicine Reports
|September 17, 2016
PubMed

Insights

Gap junction inhibition with heptanol reduced cardiac conduction velocity, leading to ventricular tachycardia in mouse hearts. This highlights the role of conduction velocity and excitation wavelength in arrhythmogenesis.

Area of Science:

  • Cardiovascular Physiology
  • Electrophysiology
  • Pharmacology

Background:

  • Gap junctions are crucial for cardiac electrical impulse propagation.
  • Dysfunction of gap junctions is implicated in cardiac arrhythmias.
  • Heptanol is a known inhibitor of gap junction communication.

Purpose of the Study:

  • To investigate the arrhythmogenic effects of the gap junction inhibitor heptanol.
  • To determine the impact of heptanol on cardiac electrophysiological parameters.
  • To elucidate the role of gap junction inhibition in the induction of ventricular tachycardia.

Main Methods:

  • Langendorff-perfused mouse hearts were used.
  • Monophasic action potentials were recorded from the left ventricular epicardium.
  • Right ventricular pacing and S1S2 stimulation protocols were applied before and after heptanol treatment.

Main Results:

  • Heptanol (0.05 mM) induced ventricular tachycardia in 6/12 hearts.
  • Heptanol significantly increased activation latencies and reduced conduction velocity (CV).
  • Action potential durations and effective refractory periods remained unchanged, but excitation wavelength (λ) was reduced.

Conclusions:

  • Low-dose heptanol alone is sufficient to induce ventricular tachycardia in mouse hearts.
  • Reduced CV and consequently decreased excitation wavelength (λ) are critical factors in promoting arrhythmogenic tendency.
  • Inhibition of gap junctions plays a central role in the development of cardiac arrhythmias.

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