Role of gap junction channel in the development of beat-to-beat action potential repolarization variability and arrhythmias

János Magyar, Tamás Bányász, Norbert Szentandrássy, Kornél Kistamás, Péter P. Nánási, Jonathan Satin

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

The short-term beat-to-beat variability of cardiac action potential duration (SBVR) occurs as a random alteration of the ventricular repolarization duration. SBVR has been suggested to be more predictive of the development of lethal arrhythmias than the action potential prolongation or QT prolongation of ECG alone. The mechanism underlying SBVR is not completely understood but it is known that SBVR depends on stochastic ion channel gating, intracellular calcium handling and intercellular coupling. Coupling of single cardiomyocytes significantly decreases the beat-to-beat changes in action potential duration (APD) due to the electrotonic current flow between neighboring cells. The magnitude of this electrotonic current depends on the intercellular gap junction resistance. Reduced gap junction resistance causes greater electrotonic current flow between cells, and reduces SBVR. Myocardial ischaemia (MI) is known to affect gap junction channel protein expression and function. MI increases gap junction resistance that leads to slow conduction, APD and refractory period dispersion, and an increase in SBVR. Ultimately, development of reentry arrhythmias and fibrillation are associated post-MI. Antiarrhythmic drugs have proarrhythmic side effects requiring alternative approaches. A novel idea is to target gap junction channels. Specifically, the use of gap junction channel enhancers and inhibitors may help to reveal the precise role of gap junctions in the development of arrhythmias. Since cell-to-cell coupling is represented in SBVR, this parameter can be used to monitor the degree of coupling of myocardium.

Original languageEnglish
Pages (from-to)1042-1052
Number of pages11
JournalCurrent Pharmaceutical Design
Volume21
Issue number8
DOIs
StatePublished - Jan 1 2015

Bibliographical note

Publisher Copyright:
© 2015 Bentham Science Publishers.

Keywords

  • Arrhythmia
  • Beat-to-beat variability
  • Gap junction
  • Heart

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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