Modulation of L-type Ca(2+) current but not activation of Ca(2+) release by the gamma(1) subunit of the dihydropyridine receptor of skeletal muscle

BACKGROUND: The multisubunit (α(1S),α(2)-δ, β(1a) and γ(1)) skeletal muscle dihydropyridine receptor (DHPR) transduces membrane depolarization into release of Ca(2+) from the sarcoplasmic reticulum (SR) and also acts as an L-type Ca(2+) channel. To more fully investigate the function of the γ(1) subunit in these two processes, we produced mice lacking this subunit by gene targeting. RESULTS: Mice lacking the DHPR γ(1) subunit (γ(1) null) survive to adulthood, are fertile and have no obvious gross phenotypic abnormalities. The γ(1) subunit is expressed at approximately half the normal level in heterozygous mice (γ(1) het). The density of the L-type Ca(2+) current in γ(1) null and γ(1) het myotubes was higher than in controls. Inactivation of the Ca(2+) current produced by a long depolarization was slower and incomplete in γ(1) null and γ(1) het myotubes, and was shifted to a more positive potential than in controls. However, the half-activation potential of intramembrane charge movements was not shifted, and the maximum density of the total charge was unchanged. Also, no shift was observed in the voltage-dependence of Ca(2+) transients. γ(1) null and γ(1) het myotubes had the same peak Ca(2+) amplitude vs. voltage relationship as control myotubes. CONCLUSIONS: The L-type Ca(2+) channel function, but not the SR Ca(2+) release triggering function of the skeletal muscle dihydropyridine receptor, is modulated by the γ(1) subunit.