title: Ion-channel blocker sensitivity of voltage-gated calcium-channel homologue Cch1 in Saccharomyces cerevisiae.
abstract: The Cch1 protein of the yeast Saccharomyces cerevisiae is a homologue of the pore-forming alpha1 subunit of mammalian voltage-gated Ca2+ channels (VGCCs), and it constitutes a high-affinity Ca2+-influx system with the Mid1 protein in this organism. Here, we characterized the kinetic property of a putative Cch1-Mid1 Ca2+ channel overexpressed in S. cerevisiae cells, and showed that the L-type VGCC blockers nifedipine and verapamil partially inhibited Cch1-Mid1 activity, but typical P/Q-, N-, R- and T-type VGCC blockers did not inhibit activity. In contrast, a third L-type VGCC blocker, diltiazem, increased Cch1-Mid1 activity. Diltiazem did not increase Ca2+ uptake in the cch1Delta and mid1Delta single mutants and the cch1Delta mid1Delta double mutant, indicating that the diltiazem-induced increase in Ca2+ uptake is completely dependent on Cch1-Mid1. These results suggest that Cch1 is pharmacologically similar to L-type VGCCs, but the interactions between Cch1 and the L-type VGCC blockers are more complicated than expected.
authors.affiliation: Laboratory of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma 371-8510, Japan.|Department of Biology, Tokyo Gakugei University, 4-1-1 Nukui kita-machi, Koganei-shi, Tokyo 184-8501, Japan.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Teng
authors.affiliation: Department of Biology, Tokyo Gakugei University, 4-1-1 Nukui kita-machi, Koganei-shi, Tokyo 184-8501, Japan.
authors.forename: Rika
authors.initials: R
authors.lastname: Goto
authors.affiliation: Biomembrane Signaling Project 2, Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8613, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Iida
authors.affiliation: Laboratory of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma 371-8510, Japan.
authors.forename: Itaru
authors.initials: I
authors.lastname: Kojima
authors.affiliation: Department of Bioenvironmental Science, Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Higashiyama 5-1, Myodaiji, Okazaki, Aichi 444-8787, Japan.|Department of Biology, Tokyo Gakugei University, 4-1-1 Nukui kita-machi, Koganei-shi, Tokyo 184-8501, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Iida
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D004110:Diltiazem / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D009543:Nifedipine / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D014700:Verapamil / Q000494:pharmacology
chemical_list: C108765:CCH1 protein, S cerevisiae; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; C090463:MID1 protein, S cerevisiae; D008562:Membrane Glycoproteins; D029701:Saccharomyces cerevisiae Proteins; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine; D002118:Calcium