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 alpha1 subunit. We describe the first functional characterization of a mutation in this gene. This alpha1 subunit mediates the dihydropyridine-sensitive calcium channel current in larval muscle but does not contribute to the amiloride-sensitive current in that tissue. A mutation, which changes a highly conserved Cys to Tyr in transmembrane domain IS1, identifies a residue important for channel function not only in Drosophila muscle but also in mammalian cardiac channels. In both cases, mutations in this Cys residue slow channel activation and reduce expressed currents. Amino acid substitutions at this Cys position in the cardiac alpha1 subunit show that the size of the side chain, rather than its ability to form disulfide bonds, affects channel activation.
Ren
D
D
Department of Biochemical Pharmacology, State University of New York at Buffalo, Buffalo, New York 14260-1200, USA.
Xu
H
H
Eberl
D F
DF
Chopra
M
M
Hall
L M
LM
D000584:Amiloride / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000235:genetics* / Q000378:metabolism; D003545:Cysteine; D004095:Dihydropyridines / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism; D004553:Electric Conductivity; D015870:Gene Expression / Q000502:physiology; D007700:Kinetics; D007814:Larva / Q000737:chemistry / Q000378:metabolism; D008322:Mammals; D008969:Molecular Sequence Data; D009132:Muscles / Q000737:chemistry / Q000378:metabolism; D016296:Mutagenesis; D009206:Myocardium / Q000737:chemistry* / Q000378:metabolism; D009865:Oocytes / Q000502:physiology; D018408:Patch-Clamp Techniques; D017354:Point Mutation / Q000502:physiology*; D011817:Rabbits; D014981:Xenopus
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D004232:Diuretics; D000584:Amiloride; D004110:Diltiazem; D003545:Cysteine