Please use this identifier to cite or link to this item: http://hdl.handle.net/1959.13/25420

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Title
Coupled calcium release channels and their regulation by luminal and cytosolic ions
Author/Creator
Laver, Derek Rowland
Description
Contraction in skeletal and cardiac muscle occurs when Ca2+ is released from the sarcoplasmic reticulum (SR) through ryanodine receptor (RyR) Ca2+ release channels. Several isoforms of the RyR exist throughout the animal kingdom, which are modulated by ATP, Ca2+ and Mg2+ in the cytoplasm and by Ca2+ in the lumen of the SR. This review brings to light recent findings on their mechanisms of action in the mammalian isoforms RyR-1 and RyR-2 with an emphasis on RyR-1 from skeletal muscle. Cytoplasmic Mg2+ is a potent RyR antagonist that binds to two classes of cytoplasmic site, identified as low-affinity, non-specific inhibition sites and high-affinity Ca2+ activation sites (A-sites). Mg2+ inhibition at the A-sites is very sensitive to the cytoplasmic and luminal milieu. Cytoplasmic Ca2+ Mg2+ and monovalent cations compete for the A-sites. In isolated RyRs, luminal Ca2+ alters the Mg2+ affinity of the A-site by an allosteric mechanism mediated by luminal sites. However, in close-packed RyR arrays luminal Ca2+ can also compete with cytoplasmic ions for the A-site. Activation of RyRs by luminal Ca2+ has been attributed to either Ca2+ feedthrough to A-sites or to Ca2+ regulatory sites on the luminal side of the RyR. As yet there is no consensus on just how luminal Ca2+ alters RyR activation. Recent evidence indicates that both mechanisms operate and are likely to be important. Allosteric regulation of A-site Mg2+ affinity could trigger Ca2+ release, which is reinforced by Ca2+ feedthrough.
Relation
European Biophysics Journal with Biophysics Letters Vol. 34, no. 5, p. 359-368
Date
2005
Publisher
Springer-Verlag
Keyword(s)
ryanodine receptor;  magnesium;  calcium;  skeletal muscle;  lipid bilayer;  cardiac sarcoplasmic-reticulum;  skeletal-muscle fibers;  ryanodine;  receptor complex;  junctional terminal cisternae;  ca2+ release;  ca-2+;  release;  ca2+-release channel;  inactivation sites;  mg2+ inhibition;  lipid-bilayers
Resource Type
journal article
Identifier
http://hdl.handle.net/1959.13/25420
Identifier
ISSN:1432-1017
Language
eng
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"European Biophysics Journal with Biophysics Letters"
 
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