Mitochondrial Depolarization and Electrophysiological Changes During Ischemia in the Rabbit and Human Heart

Am J Physiol Heart Circ Physiol. 2014 Oct 15;307(8):H1178-86. doi: 10.1152/ajpheart.00437.2014. Epub 2014 Aug 15.

Abstract

Instability of the inner mitochondrial membrane potential (ΔΨm) has been implicated in electrical dysfunction, including arrhythmogenesis during ischemia-reperfusion. Monitoring ΔΨm has led to conflicting results, where depolarization has been reported as sporadic and as a propagating wave. The present study was designed to resolve the aforementioned difference and determine the unknown relationship between ΔΨm and electrophysiology. We developed a novel imaging modality for simultaneous optical mapping of ΔΨm and transmembrane potential (Vm). Optical mapping was performed using potentiometric dyes on preparations from 4 mouse hearts, 14 rabbit hearts, and 7 human hearts. Our data showed that during ischemia, ΔΨm depolarization is sporadic and changes asynchronously with electrophysiological changes. Spatially, ΔΨm depolarization was associated with action potential duration shortening but not conduction slowing. Analysis of focal activity indicated that ΔΨm is not different within the myocardium where the focus originates compared with normal ventricular tissue. Overall, our data suggest that during ischemia, mitochondria maintain their function at the expense of sarcolemmal electrophysiology, but ΔΨm depolarization does not have a direct association to ischemia-induced arrhythmias.

Keywords: arrhythmia; imaging; ischemia; metabolism.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials*
  • Animals
  • Humans
  • Membrane Potential, Mitochondrial*
  • Mice
  • Mitochondria / metabolism
  • Mitochondria / physiology
  • Myocardial Ischemia / metabolism*
  • Myocardial Ischemia / physiopathology
  • Optical Imaging / methods
  • Rabbits