Mechanisms underlying variations in excitation-contraction coupling across the mouse left ventricular free wall

Keith W. Dilly, Charles F. Rossow, V. Scott Votaw, James S. Meabon, Jennifer L. Cabarrus, Luis Fernando Santana

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Ca2+ release during excitation-contraction (EC) coupling varies across the left ventricular free wall. Here, we investigated the mechanisms underlying EC coupling differences between mouse left ventricular epicardial (Epi) and endocardial (Endo) myocytes. We found that diastolic and systolic [Ca2+]i was higher in paced Endo than in Epi myocytes. Our data indicated that differences in action potential (AP) waveform between Epi and Endo cells only partially accounted for differences in [Ca2+]i. Rather, we found that the amplitude of the [Ca2+]i transient, but not its trigger - the Ca2+current - was larger in Endo than in Epi cells. We also found that spontaneous Ca2+ spark activity was about 2.8-fold higher in Endo than in Epi cells. Interestingly, ryanodine receptor type 2 (RyR2) protein expression was nearly 2-fold higher in Endo than in Epi myocytes. Finally, we observed less Na+-Ca2+ exchanger function in Endo than in Epi cells,which was associatedwith decreasedCa2+ efflux during the AP; this contributed to higher diastolic [Ca2+]i and SR Ca2+ in Endo than in Epi cells during pacing. We propose that transmural differences in AP waveform, SR Ca2+ release, and Na+-Ca2+ exchanger function underlie differences in [Ca2+]i and EC coupling across the left ventricular free wall.

Original languageEnglish (US)
Pages (from-to)227-241
Number of pages15
JournalJournal of Physiology
Volume572
Issue number1
DOIs
StatePublished - Apr 2006
Externally publishedYes

ASJC Scopus subject areas

  • Physiology

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