The creatine kinase system is essential for optimal refill of the sarcoplasmic reticulum Ca2+ store in skeletal muscle.
SourceJournal of Biological Chemistry, 277, 7, (2002), pp. 5275-84
Article / Letter to editor
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Cell Biology (UMC)
Journal of Biological Chemistry
SubjectStudy of abnormal differentiation and transformation processes in heritable and acquired disorders with the use of cell and animal models; Regulation of salt and water reabsorption in the renal collecting duct; Routing of proteins in polarized cells; Signal Transduction and Ion Transport; Bestudering van abnormale differentiatie en transformatieprocessen bij erfelijke of verworven aandoeningen m.b.v. cel- en diermodellen; Regulatie water en zouttransport in de verzamelbuis van de nier; Routing van eiwitten in gepolariseerde cellen; Signaaltransductie en ionentransport
Muscle function depends on an adequate ATP supply to sustain the energy consumption associated with Ca(2+) cycling and actomyosin sliding during contraction. In this regulation of energy homeostasis, the creatine kinase (CK) circuit for high energy phosphoryl transfer between ATP and phosphocreatine plays an important role. We earlier established a functional connection between the activity of the CK system and Ca(2+) homeostasis during depolarization and contractile activity of muscle. Here, we show how CK activity is coupled to the kinetics of spontaneous and electrically induced Ca(2+) transients in the sarcoplasm of myotubes. Using the UV ratiometric Ca(2+) probe Indo-1 and video-rate confocal microscopy in CK-proficient and -deficient cultured cells, we found that spontaneous and electrically induced transients were dependent on ryanodine-sensitive Ca(2+) release channels, sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase pumps, extracellular calcium, and functional mitochondria in both cell types. However, at increasing sarcoplasmic Ca(2+) load (induced by electrical stimulation at 0.1, 1, and 10 Hz), the Ca(2+) removal rate and the amount of Ca(2+) released per transient were gradually reduced in CK-deficient (but not wild-type) myotubes. We conclude that the CK/phosphocreatine circuit is essential for efficient delivery of ATP to the sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase pumps and thereby directly influences sarcoplasmic reticulum refilling and the kinetics of the sarcoplasmic Ca(2+) signals.
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