Ion-channel blocker sensitivity of voltage-gated calcium-channel homologue Cch1 in Saccharomyces cerevisiae

Microbiology (Reading). 2008 Dec;154(Pt 12):3775-3781. doi: 10.1099/mic.0.2008/021089-0.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Calcium / metabolism
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channels / drug effects
  • Calcium Channels / genetics
  • Calcium Channels / metabolism*
  • Calcium Channels, L-Type / drug effects
  • Calcium Channels, L-Type / genetics
  • Calcium Channels, L-Type / metabolism*
  • Diltiazem / pharmacology
  • Humans
  • Kinetics
  • Membrane Glycoproteins / drug effects
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Molecular Sequence Data
  • Mutation
  • Nifedipine / pharmacology
  • Saccharomyces cerevisiae / drug effects*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / drug effects
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Up-Regulation
  • Verapamil / pharmacology

Substances

  • CCH1 protein, S cerevisiae
  • Calcium Channel Blockers
  • Calcium Channels
  • Calcium Channels, L-Type
  • MID1 protein, S cerevisiae
  • Membrane Glycoproteins
  • Saccharomyces cerevisiae Proteins
  • Verapamil
  • Diltiazem
  • Nifedipine
  • Calcium