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Investigation of the effect of inositol trisphosphate in skinned skeletal muscle fibres with functional excitation-contraction coupling

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Summary

The effect of inositol trisphosphate (IP3) was investigated in mechanically skinned fibres which had the endogenous level of sarcoplasmic reticulum (SR) Ca2+ and in which the normal excitation-contraction (E-C) coupling mechanism was still functional. Application of 50 or 100 μM IP3 failed to induce a detectable force response in any such skinned fibre from either the extensor digitorum longus muscle of the rat or iliofibularis muscle of the toad, irrespective of whether the fibre was: (a) in its normally polarized, resting state; (b) chronically depolarized to inactivate the voltage sensors; (c) paralysed with D600; or (d) depolarized to threshold for force activation. Furthermore, the size of the response to subsequent depolarization or exposure to caffeine (2 mM) or reduced myoplasmic [Mg2+] indicated that little if any Ca2+ had been lost from the SR during the period of IP3 exposure (≥1 min). Also, IP3 did not induce a detectable force response when SR Ca2+ uptake was potently inhibited with 20 μM TBQ. Exposure to IP3 (50 μM) slightly potentiated the peak force response to depolarization in toad fibres, and this was probably because of an accompanying small increase in Ca2+ sensitivity of the contractile apparatus. These results appear inconsistent with the proposal that IP3 acts as the second messenger in E-C coupling in skeletal muscle.

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Posterino, G.S., Lamb, G.D. Investigation of the effect of inositol trisphosphate in skinned skeletal muscle fibres with functional excitation-contraction coupling. Journal of Muscle Research and Cell Motility 19, 67–74 (1998). https://doi.org/10.1007/BF03257391

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