A MUTATION AFFECTING DIHYDROPYRIDINE-SENSITIVE CURRENT LEVELS AND ACTIVATION KINETICS IN DROSOPHILA MUSCLE AND MAMMALIAN HEART CALCIUM CHANNELS

The Dmca1D gene encodes a Drosophila calcium channel alpha(1) subunit. We describe the first functional characterization of a mutation in th is gene, This alpha(1) subunit mediates the dihydropyridine-sensitive calcium channel current in larval muscle but does not contribute to th e amiloride-sensitive ca!rent in that tissue, A mutation, which change s a highly conserved Cys to Tyr in transmembrane domain IS1, identifie s a residue important for channel function not only in Drosophila musc le but also in mammalian cardiac channels. In both cases, mutations in this Cys residue slow channel activation and reduce expressed current s. Amino acid substitutions at this Cys position in the cardiac alpha( 1) subunit show that the size of the side chain, rather than its abili ty to form disulfide bonds, affects channel activation.