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Biphasic changes in cardiac excitation-contraction coupling early in chronic alcohol exposure

¹Departments of Molecular Pharmacology and Biological Chemistry and ²Medicine, Division of Cardiology, Northwestern University, Feinberg School of Medicine; and ³Department of Medical-Surgical Nursing, University of Illinois at Chicago College of Nursing, Chicago, Illinois

Submitted 27 February 2006 ; accepted in final form 26 April 2006

Although the negative inotropic effects of both acute and chronic ethanol (EtOH) exposure are well known, little is known concerning the acute-to-chronic transition of such effects. In this study, our objective was to address this question by detailing the effects that acute EtOH exposure induces on cellular excitation-contraction (EC) coupling and, subsequently, comparing whether and how such changes translate to the early chronic EtOH condition in a rat model known to develop alcohol-induced cardiomyopathy. Acute EtOH exposure, as formerly reported, indeed induced dose-dependent negative inotropic changes in cellular EC coupling, manifest as reductions in cell shortening, Ca²⁺ transient amplitude, Ca²⁺ decay rate, and sarcoplasmic reticulum Ca²⁺ content of isolated rat ventricular cardiac myocytes. Supplementary to this, we found Ca²⁺ spark character not to be significantly affected by acute EtOH exposure. In contrast, the results obtained from cardiac myocytes isolated from rats fed a diet containing 9% (vol/vol) EtOH for 1 mo revealed changes in these parameters reflecting positive inotropy, whereas at 3 mo, these parameters again reflected negative inotropy similar but not identical to that induced by acute EtOH exposure. No significant changes were evident at either 1- or 3-mo chronic EtOH administration in echocardiographic parameters known to be perturbed in alcoholic cardiomyopathy (ACM), thus indicating that we were examining an asymptomatic stage in chronic EtOH administration consistent with an acute-to-chronic transition phase. Continued study of such transition-phase events should provide important insight into which molecular-cellular components of EC coupling play pivotal roles in EtOH-induced disease processes, such as ACM.

rat cardiac myocytes; calcium transients; calcium sparks; confocal calcium imaging

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