title: Identification and molecular localization of a pH-sensing domain for the inward rectifier potassium channel HIR.
abstract: Inward rectifier potassium channels are found in the heart and CNS, where they are critical for the modulation and maintenance of cellular excitability. We present evidence that the inward rectifier potassium channel HIR is modulated by extracellular pH in the physiological range. We show that proton-induced changes in HIR single-channel conductance underlie the HIR pH sensitivity seen on the macroscopic level. We used chimeric and mutant channels to localize the molecular determinant of HIR pH sensitivity to a single residue, H117, in the M1-to-H5 linker region. This residue provides a molecular context that allows a titratable group to influence pore properties. We present evidence that this titratable group is one of two cysteines located in the M1-to-H5 and H5-to-M2 linkers.
authors.affiliation: Department of Biological Sciences, University of California, Santa Barbara 93106, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Coulter
authors.forename: F
authors.initials: F
authors.lastname: Périer
authors.forename: C M
authors.initials: CM
authors.lastname: Radeke
authors.forename: C A
authors.initials: CA
authors.lastname: Vandenberg
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003545:Cysteine; D004553:Electric Conductivity; D015870:Gene Expression; D006639:Histidine; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009865:Oocytes / Q000502:physiology; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011522:Protons; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D013329:Structure-Activity Relationship; D013439:Sulfhydryl Reagents / Q000494:pharmacology; D014982:Xenopus laevis; D015032:Zinc / Q000494:pharmacology
chemical_list: D015221:Potassium Channels; D011522:Protons; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D013439:Sulfhydryl Reagents; D006639:Histidine; D015032:Zinc; D003545:Cysteine