Rem inhibits skeletal muscle EC coupling by reducing the number of functional L-type Ca2+ channels.

In skeletal muscle, the L-type voltage-gated Ca(2+) channel (1,4-dihydropyridine receptor) serves as the voltage sensor for excitation-contraction (EC) coupling. In this study, we examined the effects of Rem, a member of the RGK (Rem, Rem2, Rad, Gem/Kir) family of Ras-related monomeric GTP-binding proteins, on the function of the skeletal muscle L-type Ca(2+) channel. EC coupling was found to be weakened in myotubes expressing Rem tagged with enhanced yellow fluorescent protein (YFP-Rem), as assayed by electrically evoked contractions and myoplasmic Ca(2+) transients. This impaired EC coupling was not a consequence of altered function of the type 1 ryanodine receptor, or of reduced Ca(2+) stores, since the application of 4-chloro-m-cresol, a direct type 1 ryanodine receptor activator, elicited myoplasmic Ca(2+) release in YFP-Rem-expressing myotubes that was not distinguishable from that in control myotubes. However, YFP-Rem reduced the magnitude of L-type Ca(2+) current by approximately 75% and produced a concomitant reduction in membrane-bound charge movements. Thus, our results indicate that Rem negatively regulates skeletal muscle EC coupling by reducing the number of functional L-type Ca(2+) channels in the plasma membrane.