Gap junction modifiers regulate electrical activities of the sinoatrial node and pulmonary vein: Therapeutic implications in atrial arrhythmogenesis

Chien Jung Chang, Chen Chuan Cheng, Yao Chang Chen, Yu Hsun Kao, Shih Ann Chen, Yi Jen Chen

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background Gap junction (GJ) dysfunctions predispose cardiac tissues to various arrhythmias. Sinoatrial node (SAN) and pulmonary veins (PVs) are closely related atrial dysrhythmia. This study evaluated whether GJ modifications modulate SAN and PVs electrical activities. Methods Conventional microelectrodes were used to record action potentials in isolated rabbit SAN, PVs, and connected PV-SAN tissue preparations before and after heptanol (GJ inhibitor) and PQ1 (GJ enhancer) administration with and without isoproterenol. A whole-cell patch clamp was used to record the electrical activities before and after heptanol in single SAN and PV cardiomyocytes. Results Heptanol (1, 3, and 10 μM) reduced the spontaneous beating rates of isolated SAN preparations but not PVs. Heptanol (10 μM) decelerated the SAN leading rhythm in the PV-SAN preparations and induced PV burst firings without (3 of 6, 50%) and with (6 of 6, 100%) isoproterenol (1 μM). Heptanol (10 μM) also reduced the spontaneous beating rates in single SAN cardiomyocyte, but not PV cardiomyocyte, with a decreased pacemaker current. PQ1 (50 and 500 nM) treatment did not change the spontaneous beating rates in isolated SAN and PV preparations. In the connected PV-SAN preparations, PQ1 (500 nM) did not induce any PV firing even having additional isoproterenol treatment (1 μM). Moreover, PQ1 (500 nM) prevented heptanol-induced electrical changes in SAN and PVs preparations. Conclusion GJ dysfunction modulates SAN and PV electrical activity, which may contribute to atrial arrhythmogenesis. GJ enhancer has a therapeutic potential in SAN dysfunction and atrial arrhythmogenesis.

Original languageEnglish
Pages (from-to)529-536
Number of pages8
JournalInternational Journal of Cardiology
Volume221
DOIs
Publication statusPublished - Oct 15 2016

    Fingerprint

Keywords

  • Atrial fibrillation
  • Gap junction
  • Pacemaker current
  • PQ1
  • Pulmonary vein
  • Sinoatrial node

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this