ISSN:
1432-2013
Keywords:
Skeletal muscle
;
Skinned fibres
;
Tension activation
;
Excitation-contraction coupling
;
GTP γ S
;
G-Proteins
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract We have investigated the involvement of G-proteins in excitation-contraction coupling of fast-twitch skeletal muscle, using a fibre preparation designed to retain intact T-tubules and sarcoplasmic reticulum. The nonhydrolysable analogue of guanosine triphosphate, GTP γ S (50–500 μM) caused a strong, transient isometric contraction in this preparation. Reduction of ethylene-bis(oxonitrilo) tetraacetete (EGTA) in the sealed T-tubules from 5 mM to 0.1 mM lowered the threshold to GTP γ S and removal of sodium reversibly raised it. The dihydropyridine (DHP) calcium channel antagonists nicardipine and nifedipine allowed a first contraction and then blocked subsequent GTP γ S action. The phenylalkylamine methoxyverapamil (D-600) did likewise, reversibly, at 10° C. The guanosine diphosphate analogue, GDP β S, and procaine reversibly blocked the action of GTP γ S pertussis toxin also blocked it. Photolytic release of 40–100 μM GTP γ S within 0.1 s from S-caged GTP γ S caused contraction after a latent period of 0.3–20 s. We conclude that GTP γ S can activate contraction in frog skeletal muscle via a route requiring both the integrity of the T-tubular DHP-sensitive calcium channel (DHPr) and the presence of sodium in the sealed T-tubules. We propose that in this preparation GTP γ S activates a G-protein, which in turn activates the DHPr as a calcium channel and releases stored calcium from within the sealed T-tubule. Implications of these results for the excitation-contraction coupling mechanism in skeletal muscle are discussed.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00370462
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