Normalization of current kinetics by interaction between the alpha 1 and beta subunits of the skeletal muscle dihydropyridine-sensitive Ca2+ channel.

PURIFICATION of skeletal muscle dihydropyridine binding sites has enabled protein complexes to be isolated from which Ca2+ currents have been reconstituted. Complementary DNAs encoding the five subunits of the dihydropyridine receptor, α1, β, γ, α2 and δ (ref. 1), have been cloned2–6 and it is now recognized that α2 and δ are derived from a common precursor7,8. The α1, subunit can itself produce Ca2+ currents, as was demonstrated using mouse L cells lacking α2δ (refs 9,10), β (ref. 10) and γ (our unpublished results). In L cells, stable expression of skeletal muscle α1 alone was sufficient to generate voltage-sensitive, high-threshold L-type Ca2+ channel currents which were dihydropyridine-sensitive and blocked by Cd2+, but the activation kinetics were about 100 times slower than expected for skeletal muscle Ca2+ channel currents. This could have been due to the cell type in which α1 , was being expressed or to the lack of a regulatory component particularly one of the subunits that copurifies with α1. We show here that coexpression of skeletal muscle β with skeletal muscle α1, generates cell lines expressing Ca2+ channel currents with normal activation kinetics as evidence for the participation of the dihydropyridine-receptor β subunits in the generation of skeletal muscle Ca2+ channel currents.