Functional equivalence of dihydropyridine receptor alpha1S and beta1a subunits in triggering excitation-contraction coupling in skeletal muscle.
Molecular understanding of the mechanism of excitation-contraction (EC) coupling in skeletal muscle has been made possible by cultured myotube models lacking specific dihydropyridine receptor (DHPR) subunits and ryanodine receptor type 1 (RyR1) isoforms. Transient expression of missing cDNAs in mutant myotubes leads to a rapid recovery, within days, of various Ca2+ current and EC coupling phenotypes. These myotube models have thus permitted structure-function analysis of EC coupling domains present in the DHPR controlling the opening of RyR1. The purpose of this brief review is to highlight advances made by this laboratory towards understanding the contribution of domains present in alpha1S and beta1a subunits of the skeletal DHPR to EC coupling signaling. Our main contention is that domains of the alpha1S II-III loop are necessary but not sufficient to recapitulate skeletal-type EC coupling. Rather, the structural unit that controls the EC coupling signal appears to be the alpha1S/beta1a pair.
Coronado
Roberto
R
Department of Physiology, University of Wisconsin, School of Medicine, Madison, WI 53706, USA. coronado@physiology.wisc.edu
Ahern
Chris A
CA
Sheridan
David C
DC
Cheng
Weijun
W
Carbonneau
Leah
L
Bhattacharya
Dipankar
D
D000818:Animals; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000502:physiology*; D018076:DNA, Complementary / Q000032:analysis; D004594:Electrophysiology; D018613:Microscopy, Confocal; D008954:Models, Biological; D009119:Muscle Contraction / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D018482:Muscle, Skeletal / Q000502:physiology*; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism
D020746:Calcium Channels, L-Type; D018076:DNA, Complementary; D019837:Ryanodine Receptor Calcium Release Channel