Electrophysiology of Rabbit Ventricular Myocytes Following Sustained Rapid Ventricular Pacing

Abstract

The present study examined changes in electrophysiological properties of ventricular myocytes isolated from rabbit hearts after 2–3 weeks of rapid ventricular pacing. Left ventricular end-diastolic pressure at completion of the pacing period was nearly four-fold greater than in age-matched controls, although there was no significant change in heart weight/body weight ratio. Action potentials recorded in current-clamp mode at low stimulation frequencies were significantly longer in duration and phase 1 diminished in isolated myocytes from paced hearts compared with control. In voltage-clamp experiments,l-type Ca2+current (ICa) density was not different between groups of myocytes, but the maximum current (at+10 mV) elicited by 10μmisoproterenol was approximately 40% less in myocytes from paced hearts. In contrast, maximum ICaelicited by 10μmforskolin was similar in both groups. The 4-aminopyridine-sensitive, transient outward current (Ito) was 65% less (at+60 mV) in myocytes from paced hearts than from control. However, after approximately 24 h in culture, Itodensity in these myocytes returned toward control values. Despite marked reduction in Itodensity, the inward rectifier current (IK1) was not different between groups. These data demonstrate that Itois significantly and reversibly decreased in myocytes from rapidly paced hearts, which may partly account for marked changes in action potential morphology. Although basal ICawas not altered in this group of myocytes compared with control, its modulation byβ-agonists was markedly blunted, probably through a decrease in receptor density or coupling to adenylyl cyclase. These changes in myocyte K+and Ca2+channel behavior in paced hearts may relate to impaired contractility and arrhythmogenesis that is characteristic of the intact failing heart.