title: Molecular localization of ion selectivity sites within the pore of a human L-type cardiac calcium channel.
abstract: A highly conserved position of negatively charged amino acids is present in the SS2 segments of the S5-S6 linker regions among calcium channels. We report here that replacing Glu residues at this position alters the ion selectivity of the human cardiac calcium channel. Substituting Glu334 in motif I or Glu1086 in motif III with Lys produced mutant calcium channels that permeated sodium ions 10-fold more effectively than barium ions. More conservative changes such as substitution of Glu1086 with Gln or substitution of Glu1387 with Ala also increased sodium permeation through the mutant calcium channels. Sodium currents through the mutant calcium channels could be modulated by dihydropyridines and blocked by external divalent cations. These results suggest that Glu334, Glu1086, and Glu1387 are part of a ring of glutamate residues formed in the pore-lining SS1-SS2 region and are critical in determining ion selectively and permeability of a human cardiac calcium channel.
authors.affiliation: Department of Pharmacology and Cell Biophysics, University of Cincinnati, Ohio 45267-0575.
authors.forename: S
authors.initials: S
authors.lastname: Tang
authors.forename: G
authors.initials: G
authors.lastname: Mikala
authors.forename: A
authors.initials: A
authors.lastname: Bahinski
authors.forename: A
authors.initials: A
authors.lastname: Yatani
authors.forename: G
authors.initials: G
authors.lastname: Varadi
authors.forename: A
authors.initials: A
authors.lastname: Schwartz
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D001692:Biological Transport; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D002412:Cations / Q000378:metabolism; D004594:Electrophysiology; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009206:Myocardium / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: D015220:Calcium Channels; D002412:Cations; D005971:Glutamates; D018698:Glutamic Acid