Induction of calcium currents by the expression of the α₁-subunit of the dihydropyridine receptor from skeletal muscle

Abstract

THE dihydropyridine (DHP) receptor purified from skeletal muscle comprises five protein subunits (α₁, α₂, β, γ and δ) and produces Ca²⁺ currents that are blocked by DHPs¹. Cloning of the α₁- and α₂-subunits^2,3, the former affinity-labelled by DHP, has shown that the α₁-subunit is expressed in skeletal muscle alone, whereas the α₂- and δ-subunits are also expressed in othertissues^2,4,5. Although the transient expression of the α₁-subunit in myoblasts from dysgenic mice (but not in oocytes) has been demonstrated⁶, the use of these expression systems to determine the function of the α₁-subunit is complicated by the presence of endogenous Ca²⁺ currents^7,8, which may reflect the constitutive expression of proteins similar to the α₂-, β-, γ- and/or γ-subunits. We therefore selected a cell line which has no Ca²⁺ currents or α₂-subunit, and probably no γ-subunit for stable transformation with complementary DNA of the α₁-subunit. The transformed cells express DHP-sensitive, voltage-gated Ca²⁺ channels, indicating that the minimum structure of these channels is at most an α₁βγ complex and possibly an α₁-subunit alone.