Defective excitation-contraction coupling in hearts of rats with congestive heart failure

I. Sjaastad*, J. A. Birkeland, G. Ferrier, S. Howlett, T. Skomedal, R. Bjørnerheim, J. A. Wasserstrom, O. M. Sejersted

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Aim: We examined the cellular basis for depressed cardiac contractility in rats with congestive heart failure (CHF) secondary to myocardial infarction. Methods: Six weeks after ligation of the left coronary artery, CHF was confirmed by haemodynamic measures and echocardiographic demonstration of reduced myocardial contractility in vivo. Papillary muscles from CHF animals developed less force than those from sham operated (SHAM) animals. Cell shortening was measured in isolated ventricular myocytes voltage-clamped with high resistance electrodes. Ca2+ transients were measured in fluo-4 loaded myocytes. Results: Contractions triggered by depolarizing test steps from a post conditioning potential of -70 mV were significantly smaller and had significantly reduced velocity of shortening in CHF compared with SHAM myocytes. However, contractions initiated from -40 mV, were similar in amplitude and velocity of shortening in CHF and SHAM cells. L-type Ca2+ current was not significantly different between CHF and SHAM cells, whether activated from -70 or -40 mV. Therefore, in SHAM cells, excitation-contraction coupling exhibited higher gain when contractions were initiated from negative (-70 mV), as compared with depolarized potentials (-40 mV). However, in CHF myocytes, excitation-contraction coupling gain was selectively depressed with steps from -70 mV. This depression of gain in CHF was not accompanied by a significant reduction in sarcoplasmic reticulum Ca2+ content. Isoproterenol increased Ca2+ transients less in CHF than SHAM myocytes. Conclusion: In this post-infarction model of CHF, the contractile deficit was voltage dependent and the gain of excitation-contraction coupling was selectively depressed for contractions initiated negative to -40 mV.

Original languageEnglish (US)
Pages (from-to)45-58
Number of pages14
JournalActa Physiologica Scandinavica
Volume184
Issue number1
DOIs
StatePublished - May 2005

Keywords

  • Calcium-induced calcium release
  • Congestive heart failure
  • Excitation-contraction coupling
  • Myocardial infarction

ASJC Scopus subject areas

  • Physiology

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