REDUCED CA2-MUSCLE DEFICIENT IN DIHYDROPYRIDINE RECEPTOR BETA-1 SUBUNIT( CURRENT, CHARGE MOVEMENT, AND ABSENCE OF CA2+ TRANSIENTS IN SKELETAL)

The Ca2+ currents, charge movements, and intracellular Ca2+ transients in mouse skeletal muscle cells homozygous for a null mutation in the cchb1 gene encoding the beta 1 subunit of the dihydropyridine receptor have been characterized. I-beta null, the L-type Ca2+ current of muta nt cells, had a similar to 13-fold lower density than the L-type curre nt of normal cells (0.41 +/- 0.042 pA/pF at + 20 mV, compared with 5.2 +/- 0.38 pA/pF in normal cells). I-beta null was sensitive to dihydro pyridines and had faster kinetics of activation and slower kinetics of inactivation than the L-type current of normal cells. Charge movement was reduced similar to 2.8-fold, with Q(max) = 6.9 +/- 0.61 and Q(max ) = 2.5 +/- 0.2 nC/mu F in normal and mutant cells, respectively. Appr oximately 40% of Q(max) was nifedipine sensitive in both groups. In co ntrast to normal cells, Ca2+ transients could not be detected in mutan t cells at any test potential; however, caffeine induced a robust Ca2 transient. In homogenates of mutant muscle, the maximum density of [H -3]PN200-110 binding sites (B-max) was reduced similar to 3.9-fold. Th e results suggest that the excitation-contraction uncoupling of beta(1 )-null skeletal muscle involves a failure of the transduction mechanis m that is due to either a reduced amount of alpha(1s) subunits in the membrane or the specific absence of beta(1) from the voltage-sensor co mplex.