title: Asp residues of the Glu-Glu-Asp-Asp pore filter contribute to ion permeation and selectivity of the Ca(v)3.2 T-type channel.
abstract: Voltage-activated Ca2+ channels are membrane protein machinery performing selective permeation of external calcium ions. The main Ca2+ selective filters of all high-voltage-activated Ca2+ channel isoforms are commonly composed of four Glu residues (EEEE), while those of low-voltage-activated T-type Ca2+ channel isoforms are made up of two Glu and two Asp residues (EEDD). We here investigate how the Asp residues at the pore loops of domains III and IV affect biophysical properties of the Ca(v)3.2 channel. Electrophysiological characterization of the pore mutant channels in which the pore Asp residue(s) were replaced with Glu, showed that both Asp residues critically control the biophysical properties of Ca(v)3.2, including relative permeability between Ba2+ and Ca2+, anomalous mole fraction effect (AMFE), voltage dependency of channel activation, Cd2+ blocking sensitivity, and pH effects, in distinctive ways.
authors.affiliation: Department of Life Science, Sogang University, Seoul 121-742, Republic of Korea.
authors.forename: Hyun-Jee
authors.initials: HJ
authors.lastname: Park
authors.forename: So-Jung
authors.initials: SJ
authors.lastname: Park
authors.forename: Eun-Joo
authors.initials: EJ
authors.lastname: Ahn
authors.forename: So-Young
authors.initials: SY
authors.lastname: Lee
authors.forename: Haengsoo
authors.initials: H
authors.lastname: Seo
authors.forename: Jung-Ha
authors.initials: JH
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001224:Aspartic Acid / Q000737:chemistry*; D001464:Barium / Q000378:metabolism; D002104:Cadmium / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D020747:Calcium Channels, T-Type / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D016296:Mutagenesis; D009842:Oligopeptides / Q000737:chemistry; D009865:Oocytes / Q000502:physiology; D018408:Patch-Clamp Techniques; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014981:Xenopus / Q000254:growth & development / Q000502:physiology
chemical_list: C479952:CACNA1H protein, human; D020747:Calcium Channels, T-Type; D009842:Oligopeptides; D020033:Protein Isoforms; D002104:Cadmium; D001464:Barium; D001224:Aspartic Acid; D002118:Calcium
keywords: Ca(v)3.2 T-type channel; Cd(2+) blocking sensitivity; Permeation and selectivity; Proton block; Voltage clamping