Heart failure - A challenge to our current concepts of excitation-contraction coupling

Ivar Sjaastad, J. Andrew Wasserstrom, Ole M. Sejersted*

*Corresponding author for this work

Research output: Contribution to journalReview article

43 Scopus citations

Abstract

Development of novel therapeutic strategies for congestive heart failure (CHF) seems to be hampered by insufficient knowledge of the molecular machinery of excitation-contraction (EC) coupling in both normal and failing hearts. Cardiac hypertrophy and failure represent a multitude of cardiac phenotypes, and available invasive and non-invasive techniques, briefly reviewed here, allow proper quantification of myocardial function in experimental models even in rats and mice. Both reduced fractional shortening and reduced velocity of contraction characterize myocardial failure. Only when myocardial function is depressed in vivo can meaningful studies be done in vitro of contractility and EC coupling. Also, we point out potential limitations with the whole cell patch clamp technique. Two main factors stand out as explanations for myocardial failure. First, a basic feature of CHF seems to be a reduced Ca2+ load of the sarcoplasmic reticulum (SR) mainly due to a low phosphorylation level of phospholamban. Second, there seems to be a defect of the trigger mechanism of Ca2+ release from the SR. We argue that this defect only becomes manifest in the presence of reduced Ca2+ reuptake capacity of the SR and that it may not be solely attributable to reduced gain of the Ca2+-induced Ca2+ release (CICR). We list several possible explanations for this defect that represent important avenues for future research.

Original languageEnglish (US)
Pages (from-to)33-47
Number of pages15
JournalJournal of Physiology
Volume546
Issue number1
DOIs
StatePublished - Jan 1 2003

ASJC Scopus subject areas

  • Physiology

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