Effects of Na+/Ca2+ exchange induced by SR Ca 2+ release on action potentials and afterdepolarizations in guinea pig ventricular myocytes

C. Ian Spencer, James S.K. Sham

Research output: Contribution to journalArticle

Abstract

In cardiac cells, evoked Ca2+ releases or spontaneous Ca 2+ waves activate the inward Na+/Ca2+ exchange current (INaCa), which may modulate membrane excitability and arrhythmogenesis. In this study, we examined changes in membrane potential due to INaCa elicited by sarcoplasmic reticulum (SR) Ca2+ release in guinea pig ventricular myocytes using whole cell current clamp, fluorescence, and confocal microscopy. Inhibition of INaCa by Na +-free, Li+-containing Tyrode solution reversibly abbreviated the action potential duration at 90% repolarization (APD 90) by 50% and caused SR Ca2+ overload. APD90 was similarly abbreviated in myocytes exposed to the Na+/Ca 2+ exchange inhibitor KB-R7943 (5 μM) or after inhibition of SR Ca2+ release with ryanodine (20 μM). In the absence of extracellular Na+, spontaneous SR Ca2+ releases caused minimal changes in resting membrane potential. After the myocytes were returned to Na+-containing solution, the potentiated intracellular Ca 2+ concentration ([Ca2+]i) transients dramatically prolonged APD90 and [Ca2+]i oscillations caused delayed and early afterdepolarizations (DADs and EADs). Laser-flash photolysis of caged Ca2+ mimicked the effects of spontaneous [Ca2+]i oscillations, confirming that APD prolongation, DADs, and EADs could be ascribed to intracellular Ca2+ release. These results suggest that Na+/Ca2+ exchange is a major physiological determinant of APD and that INaCa activation by spontaneous SR Ca2+ release/oscillations, depending on the timing, can account for both DADs and EADs during SR Ca2+ overload.

Original languageEnglish (US)
Pages (from-to)H2552-H2562
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume285
Issue number6 54-6
DOIs
StatePublished - Dec 2003

Keywords

  • Ca overload
  • Delayed afterdepolarization
  • Early afterdepolarization
  • Flash photolysis
  • Ischemia-reperfusion arrhythmia
  • Sarcoplasmic reticulum
  • Triggered arrhythmia

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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