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Short-Term Regulation of Excitation-Contraction Coupling by the ß_1a Subunit in Adult Mouse Skeletal Muscle

María C. García ^*, Elba Carrillo ^*, José M. Galindo ^*, Ascensión Hernández ^*, Julio A. Copello , Michael Fill  and Jorge A. Sánchez ^*

^* Departmento de Farmacología, Centro de Investigación y de Estudios Avanzados del I.P.N., Mexico, D.F. 07360, Mexico; Department of Pharmacology, Southern Illinois University, Springfield, Illinois; and Department of Physiology, Loyola University Chicago, Maywood, Illinois

Correspondence: Address reprint requests to Dr. Jorge A. Sánchez, Dept. of Pharmacology, Cinvestav Apartado Postal 14-740, Mexico, D.F. 07360. Tel.: 52-55-5061-3301; Fax: 52-55-5577-7090; E-mail: jsanchez{at}cinvestav.mx.

The ß_1a subunit of the skeletal muscle voltage-gated Ca²⁺ channel plays a fundamental role in the targeting of the channel to the tubular system as well as in channel function. To determine whether this cytosolic auxiliary subunit is also a regulatory protein of Ca²⁺ release from the sarcoplasmic reticulum in vivo, we pressure-injected the ß_1a subunit into intact adult mouse muscle fibers and recorded, with Fluo-3 AM, the intracellular Ca²⁺ signal induced by the action potential. We found that the ß_1a subunit significantly increased, within minutes, the amplitude of Ca²⁺ release without major changes in its time course. ß_1a subunits with the carboxy-terminus region deleted did not show an effect on Ca²⁺ release. The possibility that potentiation of Ca²⁺ release is due to a direct interaction between the ß_1a subunit and the ryanodine receptor was ruled out by bilayer experiments of RyR1 single-channel currents and also by Ca²⁺ flux experiments. Our data suggest that the ß_1a subunit is capable of regulating E-C coupling in the short term and that the integrity of the carboxy-terminus region is essential for its modulatory effect.