Angiotensin 1-7 modulates electrophysiological characteristics and calcium homoeostasis in pulmonary veins cardiomyocytes via MAS/PI3K/eNOS signalling pathway

Yen Yu Lu, Wen Shiann Wu, Yung Kuo Lin, Chen Chuan Cheng, Yao Chang Chen, Shih Ann Chen, Yi Jen Chen

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: Atrial fibrillation (AF) is the most common sustained arrhythmia, and pulmonary veins (PVs) play a critical role in triggering AF. Angiotensin (Ang)-(1-7) regulates calcium (Ca2+) homoeostasis and also plays a critical role in cardiovascular pathophysiology. However, the role of Ang-(1-7) in PV arrhythmogenesis remains unclear. Materials and methods: Conventional microelectrodes, whole-cell patch-clamp and the fluo-3 fluorimetric ratio technique were used to record ionic currents and intracellular Ca2+ in isolated rabbit PV preparations and in single isolated PV cardiomyocytes, before and after administration of Ang-(1-7). Results: Ang (1-7) concentration dependently (0.1, 1, 10 and 100 nmol/L) decreased PV spontaneous electrical activity. Ang-(1-7) (100 nmol/L) decreased the late sodium (Na+), L-type Ca2+ and Na+-Ca2+ exchanger currents, but did not affect the voltage-dependent Na+ current in PV cardiomyocytes. In addition, Ang-(1-7) decreased intracellular Ca2+ transient and sarcoplasmic reticulum Ca2+ content in PV cardiomyocytes. A779 (a Mas receptor blocker, 3 μmol/L), L-NAME (a NO synthesis inhibitor, 100 μmol/L) or wortmannin (a specific PI3K inhibitor, 10 nmol/L) attenuated the effects of Ang-(1-7) (100 nmol/L) on PV spontaneous electric activity. Conclusion: Ang-(1-7) regulates PV electrophysiological characteristics and Ca2+ homoeostasis via Mas/PI3K/eNOS signalling pathway.

Original languageEnglish
Pages (from-to)e12854
JournalEuropean Journal of Clinical Investigation
Volume48
Issue number1
DOIs
Publication statusPublished - Jan 1 2018

Keywords

  • Angiotensin-(1-7)
  • Calcium homoeostasis
  • Electrophysiology
  • Pulmonary vein

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry

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