Function of a truncated dihydropyridine receptor as both voltage sensor and calcium channel

Abstract

THE skeletal muscle dihydropyridine (DHP) receptor serves dual functions, as a voltage sensor for excitation–contraction coupling and as an L-type calcium channel^1–3. Biochemical analysis indicates the presence of two forms of the DHP receptor polypeptide in skeletal muscle, a full-length translation product present as a minor species and a much more abundant form that has a truncated carboxy-terminus^4–6. On the basis of these and other observations⁷, it has been proposed⁸ that, in skeletal muscle, only the full-length DHP receptor can function as a calcium channel and that the truncated form can only function as a voltage sensor for excitation–contraction coupling. To resolve this issue, we have now constructed a complementary DNA (pC6Δl) encoding a protein corresponding to the truncated DHP receptor in skeletal muscle. Expression of pC6Δl in dysgenic myotubes fully restores both excitation–contraction coupling and calcium current, consistent with the idea that a single class of DHP receptors performs both functions.