title: Control of ionic selectivity by a pore helix residue in the Kv1.2 channel.
abstract: Interaction between the selectivity filter and the adjacent pore helix of voltage-gated K(+) (Kv) channels controls pore stability during K(+) conduction. Kv channels, having their selectivity filter destabilized during depolarization, are said to undergo C-type inactivation. We examined the functionality of a residue at the pore helix of the Kv1.2 channel (V370), which reportedly affects C-type inactivation. A mutation into glycine (V370G) caused a shift in reversal potential from around -72 to -9 mV. The permeability ratios (P(Na)/P(K)) of the wild type and V370G mutant are 0.04 and 0.76, respectively. In the wild-type, P(Rb)/P(K), P(Cs)/P(K) and P(Li)/P(K) are 0.78, 0.10 and 0.05, respectively. Kv1.2 V370G channels had enhanced permeability to Rb(+) and Cs(+) (P(Rb)/P(K) and P(Cs)/P(K) are 1.63 and 1.18, respectively); however, Li(+) permeability was not significantly augmented (P(Li)/P(K) is 0.13). Therefore, in addition to its known effect on pore stability, V370 of Kv1.2 is also crucial in controlling ion selectivity.
authors.affiliation: Department of Life Sciences, National Chung Hsing University, Taichung 402, Taiwan.
authors.forename: Chia-Chia
authors.initials: CC
authors.lastname: Chao
authors.forename: Chieh-Chen
authors.initials: CC
authors.lastname: Huang
authors.forename: Chang-Shin
authors.initials: CS
authors.lastname: Kuo
authors.forename: Yuk-Man
authors.initials: YM
authors.lastname: Leung
mesh_terms: D019943:Amino Acid Substitution; D002414:Cations, Monovalent / Q000378:metabolism*; D002586:Cesium / Q000378:metabolism; D006801:Humans; D015640:Ion Channel Gating / Q000235:genetics*; D051663:Kv1.2 Potassium Channel / Q000235:genetics*; D008094:Lithium / Q000378:metabolism; D008958:Models, Molecular; D009062:Mouth Neoplasms / Q000378:metabolism; D017433:Protein Structure, Secondary; D012413:Rubidium / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D002414:Cations, Monovalent; D051663:Kv1.2 Potassium Channel; D002586:Cesium; D008094:Lithium; D012413:Rubidium