Uncoupling the mitochondria facilitates alternans formation in the isolated rabbit heart

Rebecca M. Smith, Ramjay Visweswaran, Iryna Talkachova, Jillian K. Wothe, Elena G. Tolkacheva

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Alternans of action potential duration (APD) and intracellular calcium ([Ca2+]i) transients in the whole heart are thought to be markers of increased propensity to ventricular fibrillation during ischemia-reperfusion injuries. During ischemia, ATP production is affected and the mitochondria become uncoupled, which may affect alternans formation in the heart. The aim of our study was to investigate the role of mitochondria on the formation of APD and [Ca2+]i alternans in the isolated rabbit heart. We performed dual voltage and [Ca2+]i optical mapping of isolated rabbit hearts under control conditions, global no-flow ischemia (n = 6), and after treatment with 50 nM of the mitochondrial uncoupler FCCP (n = 6). We investigated the formation of alternans of APD, [Ca2+]i amplitude (CaA), and [Ca2+]i duration (CaD) under different rates of pacing. We found that treatment with FCCP leads to the early occurrence of APD, CaD, and CaA alternans; an increase of intraventricular APD but not CaD heterogeneity; and significant reduction in conduction velocity compared with that of control. Furthermore, we demonstrated that FCCP and global ischemia have similar effects on the prolongation of [Ca2+]i transients, whereas ischemia induces a significantly larger reduction of APD compared with that in FCCP treatment. In conclusion, our results demonstrate that uncoupling of mitochondria leads to an earlier occurrence of alternans in the heart. Thus, in conditions of mitochondrial stress, as seen during myocardial ischemia, uncoupled mitochondria may be responsible for the formation of both APD and [Ca2+]i alternans in the heart, which in turn creates a substrate for ventricular arrhythmias.

Original languageEnglish (US)
Pages (from-to)H9-H18
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume305
Issue number1
DOIs
StatePublished - Jul 1 2013

Fingerprint

Action Potentials
Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone
Mitochondria
Rabbits
Ischemia
Ventricular Fibrillation
Reperfusion Injury
Myocardial Ischemia
Cardiac Arrhythmias
Adenosine Triphosphate
Calcium

Keywords

  • Action potential
  • Alternans
  • Calcium
  • FCCP
  • Ischemia
  • Mitochondria

Cite this

Uncoupling the mitochondria facilitates alternans formation in the isolated rabbit heart. / Smith, Rebecca M.; Visweswaran, Ramjay; Talkachova, Iryna; Wothe, Jillian K.; Tolkacheva, Elena G.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 305, No. 1, 01.07.2013, p. H9-H18.

Research output: Contribution to journalArticle

Smith, Rebecca M. ; Visweswaran, Ramjay ; Talkachova, Iryna ; Wothe, Jillian K. ; Tolkacheva, Elena G. / Uncoupling the mitochondria facilitates alternans formation in the isolated rabbit heart. In: American Journal of Physiology - Heart and Circulatory Physiology. 2013 ; Vol. 305, No. 1. pp. H9-H18.
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