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.
Bannister
R A
RA
Department of Physiology and Biophysics, University of Colorado-Denver, Aurora, Colorado 80045, USA .
Colecraft
H M
HM
Beam
K G
KG
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology; D002478:Cells, Cultured; D015640:Ion Channel Gating / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D020559:Monomeric GTP-Binding Proteins / Q000502:physiology*; D009119:Muscle Contraction / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000502:physiology*
D020746:Calcium Channels, L-Type; C108135:Rem protein, mouse; D020559:Monomeric GTP-Binding Proteins; D002118:Calcium