title: Mechanisms underlying variations in excitation-contraction coupling across the mouse left ventricular free wall.
abstract: Ca(2+) 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 [Ca(2+)](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 [Ca(2+)](i). Rather, we found that the amplitude of the [Ca(2+)](i) transient, but not its trigger - the Ca(2+) current - was larger in Endo than in Epi cells. We also found that spontaneous Ca(2+) 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(+)-Ca(2+) exchanger function in Endo than in Epi cells, which was associated with decreased Ca(2+) efflux during the AP; this contributed to higher diastolic [Ca(2+)](i) and SR Ca(2+) in Endo than in Epi cells during pacing. We propose that transmural differences in AP waveform, SR Ca(2+) release, and Na(+)-Ca(2+) exchanger function underlie differences in [Ca(2+)](i) and EC coupling across the left ventricular free wall.
authors.affiliation: Department of Physiology and Biophysics, University of Washington, Box 357290, Seattle, WA 98195, USA.
authors.forename: Keith W
authors.initials: KW
authors.lastname: Dilly
authors.forename: Charles F
authors.initials: CF
authors.lastname: Rossow
authors.forename: V Scott
authors.initials: VS
authors.lastname: Votaw
authors.forename: James S
authors.initials: JS
authors.lastname: Meabon
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Cabarrus
authors.forename: Luis F
authors.initials: LF
authors.lastname: Santana
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D002478:Cells, Cultured; D004699:Endocardium / Q000166:cytology / Q000502:physiology; D006329:Heart Conduction System / Q000502:physiology*; D006352:Heart Ventricles / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D009200:Myocardial Contraction / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000502:physiology*; D010496:Pericardium / Q000166:cytology / Q000502:physiology; D016276:Ventricular Function