title: Effects of extracellular cations and mutations in the pore region on the inward rectifier K+ channel IRK1.
abstract: It is known that the rectification property of the inward rectifier K+ channel, IRK1, is caused by a block of outward current by cytoplasmic Mg2+ and polyamines, and that the voltage dependence of rectification shifts according to the equilibrium potential of K+. Here it is shown that extracellular K+ (K+ o) but not intracellular K+ (K+ i) affects the activation kinetics of IRK1. A mutant in which the conserved positively charged residue arginine was replaced by a tyrosine (R148Y) exhibited slower activation and a negative shift of the conductance-voltage relationship. In addition, the conductance did not saturate at negative potentials as was observed for the wild type. When using T1+o instead of K+ o as permeant ion, the differences between the wild type and the mutant were qualitatively similar but less prominent. These results suggest that extracellular cations (e.g., K+ o or T1+ o) play a role in the activation of IRK1. Since the effects of K+ o or T1+ o were altered in the mutant, the site R148 presumably is involved in channel regulation by extracellular cations.
authors.affiliation: Department of Neurophysiology, Tokyo Metropolitan Institute for Neuroscience, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kubo
mesh_terms: D000595:Amino Acid Sequence; D002412:Cations; D002460:Cell Line; D005110:Extracellular Space; D006801:Humans; D015640:Ion Channel Gating; D008564:Membrane Potentials; D008969:Molecular Sequence Data; D009154:Mutation; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D002412:Cations; D015221:Potassium Channels