Excitation-contraction-relaxation cycle: role of Ca2+-regulatory membrane proteins in normal, stimulated and pathological skeletal muscle (review).
Extremely large protein complexes involved in the Ca2+-regulatory system of the excitation-contraction-relaxation cycle have been identified in skeletal muscle, i.e. clusters of the Ca2+-binding protein calsequestrin, apparent tetramers of Ca2+-ATPase pump units and complexes between the transverse-tubular alpha1-dihydropyridine receptor and ryanodine receptor Ca2+-release channel tetramers of the sarcoplasmic reticulum. While receptor interactions appear to be crucial for signal transduction during excitation-contraction coupling, avoidance of passive disintegration of junctional complexes and stabilization of receptor interactions may be mediated by disulfide-bonded clusters of triadin. Oligomerization of Ca2+-release, Ca2+-sequestration and Ca2+-uptake complexes appear to be an intrinsic property of these muscle membrane proteins. During chronic low-frequency stimulation, the expression of triad receptors is decreased while conditioning has only a marginal effect on Ca2+-binding proteins. In contrast, muscle stimulation induces a switch from the fast-twitch Ca2+-ATPase to its slow-twitch/cardiac isoform. These alterations in Ca2+-handling might reflect early functional adaptations to electrical stimulation. Studying Ca2+-homeostasis in transformed muscles is important regarding the evaluation of new clinical applications such as dynamic cardiomyoplasty. Studies of Ca2+-handling in skeletal muscle fibers have not only increased our understanding of muscle regulation, but have given important insights into the molecular pathogenesis of malignant hyperthermia, hypokalemic periodic paralysis and Brody disease.
Murray
B E
BE
Department of Pharmacology, University College Dublin, Belfield, Dublin 4, Ireland.
Froemming
G R
GR
Maguire
P B
PB
Ohlendieck
K
K
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D009119:Muscle Contraction / Q000502:physiology*; D009126:Muscle Relaxation; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009135:Muscular Diseases / Q000378:metabolism* / Q000473:pathology; D012016:Reference Values; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
D008565:Membrane Proteins; D002118:Calcium