Transmural Gradients of Repolarization and Excitation–Contraction Coupling in Mouse Ventricle

Abstract

See related article, pages 1306–1313 The effects of changes in action potential waveform on excitation–contraction coupling in mammalian ventricle were first identified almost 40 years ago.1 Many important details concerning the relationship between action potential duration and tension development have been elucidated.2 Recent work has demonstrated significant effects on the intracellular Ca transient and excitation–contraction coupling of early repolarization of the action potential, which is strongly regulated by a Ca2+-independent transient outward K+ current denoted I to.3–6 The molecular physiology and some aspects of the pharmacology of this current are now quite well understood, based, in part, on a series of comprehensive articles from the Nerbonne et al,7,8 Strauss and Campbell,9 and others.6 Interestingly, a somewhat similar transient outward K+ current is expressed in neurons10 and in selected regions near the intraventricular septum of mammalian hearts.11–13 One of the most striking features of the transient outward K+ current in mammalian ventricle is the difference in its transmural expression, with significantly higher expression levels in epi- than in endocardium14 (see also references 8, 9, 11). The basis for this transmural heterogeneity, and also for the higher levels of expression in the right ventricle compared with the left, continues to be a topic of intense investigation. Significant new information and plausible working hypotheses for the way in which this heterogeneity …