Angiotensin II induces complex fractionated electrogram in a cultured atrial myocyte monolayer mediated by calcium and sodium-calcium exchanger

Chia Ti Tsai, Fu Tien Chiang, Wen Pin Chen, Juey Jen Hwang, Chuen Den Tseng, Cho Kai Wu, Chih Chieh Yu, Yi Chih Wang, Ling Ping Lai, Jiunn Lee Lin

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Angiotensin II (AngII) has been implicated in the mechanism of atrial fibrillation (AF). There may be calcium-dependent pro-fibrillatory effect of AngII on atrial myocytes. We used cultured confluent HL-1 atrial myocyte monolayer with spontaneously propagated depolarization to study direct pro-fibrillatory effect of AngII and its molecular mechanism. AngII stimulation induced fibrillatory-like complex electrogram and calcium wave propagation. AngII shortened action potential duration and augmented calcium transient, thus increasing electrochemical gradient of forward-mode sodium-calcium exchanger (NCX) current and induced frequent irregular afterdepolarizations. AngII increased expression of sodium-calcium exchanger (NCX), further increasing calcium-membrane voltage coupling gain. The fibrillatory effect of AngII was attenuated by NCX blocker SEA0400 and NCX siRNA knockdown. AngII increased expression of L-type calcium channel and augmented calcium transient through PKC and CREB. The fibrillatory effect of AngII was also attenuated by PKC inhibitor chelerythrine and dominant negative form of CREB. In conclusions, AngII itself may electrically contribute to the mechanism of AF through increasing NCX expression and augmenting calcium transient, which is PKC and CREB dependent. Specific genetic knockdown of NCX attenuated calcium mediated afterdepolarization and complex electrogram.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalCell Calcium
Volume49
Issue number1
DOIs
Publication statusPublished - Jan 1 2011
Externally publishedYes

Keywords

  • Angiotensin II
  • Atrial fibrillation
  • Cardiomyocyte monolayer
  • Signal transduction
  • Sodium-calcium exchanger

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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