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Exp Clin Cardiol. 2005 Fall;10(3):196-9.

The role of ryanodine receptors and consequences of their alterations during cardiac insufficiency.

Author information

  • 1INSERM U-637, Physiopathologie Cardiovasculaire, CHU Arnaud de Villeneuve, Montpellier, France.

Abstract

Congestive heart failure (CHF) is a leading cause of death. Although changes to other components contribute, it is generally agreed that much of the contractile deficit is due to reduced Ca(2+) homeostasis that includes alterations in Ca(2+) current and action potential characteristics, together with reduced Ca(2+) transient amplitude. CHF is also associated with progressive skeletal muscle dysfunction. In both cardiac and skeletal muscles, the global increase in myoplasmic Ca(2+) during depolarization, or Ca(2+) transient, appears to consist of the summation of large numbers of local, unitary Ca(2+) release events (ie, Ca(2+) sparks) resulting from the activity of a cluster of ryanodine receptors (RyRs) (ie, RyR1 or RyR2 in skeletal and cardiac muscles, respectively). RyR2 channels from failing hearts have been shown to be hyperphosphorylated by protein kinase A, leading to dissociation of FK506-binding protein 12.6 and altered RyR2 channel function. After reviewing the alterations occurring in cardiomyocytes, the present report summarizes the intrinsic alterations of Ca(2+) homeostasis in rat extensor digitorum longus skeletal muscle. They include a weaker and prolonged Ca(2+) transient that could be attributed to both a lower synchronization of the individual Ca(2+) sparks and a lower synchronization of these events triggered upon depolarization. As in cardiac muscle, these alterations in sarcoplasmic reticulum function are associated with protein kinase A-induced hyperphosphorylation of RyR1 and a concomitant reduction in FK506-binding protein 12. These specific alterations in RyR1-dependent Ca(2+) release could play a significant role in the specific force decrements in skeletal muscle as well as in the remodelling that occurs secondary to CHF.

KEYWORDS:

Calcium sparks; Heart failure; Mammalian skeletal muscle; Multiphoton microscopy

PMID:
19641687
[PubMed]
PMCID:
PMC2716251
Free PMC Article
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