Electrophysiology of rabbit ventricular myocytes following sustained rapid ventricular pacing

George J. Rozanski, Zhi Xu, Ryan T. Whitney, Hiroshi Murakami, Irving H. Zucker

Research output: Contribution to journalArticle

72 Scopus citations

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 (I(Ca)) density was not different between groups of myocytes, but the maximum current (at +10 mV) elicited by 10 μM isoproterenol was approximately 40% less in myocytes from paced hearts. In contrast, maximum I(Ca) elicited by 10 μM forskolin was similar in both groups. The 4-aminopyridine-sensitive, transient outward current (I(Ca)) was 65% less (at +60 mV) in myocytes from paced hearts than from control. However, after approximately 24 h in culture, I(to) density in these myocytes returned toward control values. Despite marked reduction in I(to) density, the inward rectifier current (I(K1)) was not different between groups. These data demonstrate that I(to) is significantly and reversibly decreased in myocytes from rapidly paced hearts, which may partly account for marked changes in action potential morphology. Although basal I(Ca) was not altered in this group of myocytes compared with control, its modulation by β-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.

Original languageEnglish (US)
Pages (from-to)721-732
Number of pages12
JournalJournal of Molecular and Cellular Cardiology
Volume29
Issue number2
DOIs
StatePublished - Feb 1997

Keywords

  • Ca channels
  • Heart failure
  • K channels
  • β-responsiveness

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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