IMR Press / FBL / Volume 7 / Issue 4 / DOI: 10.2741/lamb

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article

Voltage-sensor control of Ca2+ release in skeletal muscle: insights from skinned fibers

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1 Department of Zoology, La Trobe University, Melbourne, Victoria, 3086, Australia
Academic Editor:Hector Valdivia
Front. Biosci. (Landmark Ed) 2002, 7(4), 834–842;
Published: 1 April 2002
(This article belongs to the Special Issue The structure and function of calcium release channels)

Important aspects of the excitation-contraction (EC) coupling process in skeletal muscle have been revealed using mechanically-skinned fibers in which the transverse-tubular system can be depolarized by ion substitution or electrical stimulation, activating the voltage-sensors which in turn open the Ca2+ release channels in the adjacent sarcoplasmic reticulum (SR). Twitch and tetanic force responses elicited in skinned fibers closely resemble those in intact fibers, showing that the coupling mechanism is entirely functional. It was found that ATP has to be bound to the Ca2+ release channels for them to be activated by the voltage-sensors and that the coupling mechanism likely involves the voltage-sensors removing the inhibitory effects of cytoplasmic Mg2+ on the release channels; such findings are relevant to the basis of muscle fatigue and to certain diseases such as malignant hyperthermia (MH). EC coupling is evidently not mediated by upmodulation of Ca2+-induced Ca2+ release (CICR) or by an oxidation or phosphorylation reaction. The Ca2+ load in the SR of skinned fibers can be set at the endogenous level or otherwise. The normal coupling mechanism functions well in mammalian fast-twitch fibers even when the SR is only partially loaded, whereas CICR is highly dependent on SR luminal Ca2+ and caffeine is poorly effective at inducing release at the endogenous SR Ca2+ load level.

Cell Physiology
Skeletal Muscle
Ca2+ Release
Excitation-Contraction Coupling
Skinned Fiber
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