title: Identification of domains of the cardiac inward rectifying K+ channel, CIR, involved in the heteromultimer formation and in the G-protein gating.
abstract: The cardiac inward rectifying K+ channel, CIR, and the strongly inward rectifying K+ channel, IRK1, exhibited clearly different electrophysiological properties. CIR formed a heteromultimer with the G-protein coupled inward rectifying K+ channel, GIRK1, whereas IRK1 did not, and CTR homo- and heteromultimeric channels were activated by G-protein beta 1 gamma 2 subunits (G beta 1 gamma 2), whereas IRK1 channels were not. To identify the domains of CIR involved in the heteromultimer formation with GIRK1 and in the G beta 1 gamma 2 gating, we constructed chimeras of CIR and IRK1 and examined their electrophysiological properties. The channels were divided into three domains; the N-terminal cytoplasmic domain, the C-terminal cytoplasmic domain and the residual core domain. By the analysis, it was concluded that (i) the core region of CIR, but not the N and C cytoplasmic domains, is critical for the heteromultimer formation with GIRK1; and (ii) the N and C terminal cytoplasmic regions of CIR are sufficient for the G beta 1 gamma 2 gating. We also showed that the N terminal cytoplasmic region is involved in the determination of the rate of activation upon hyperpolarization.
authors.affiliation: Department of Neurophysiology, Tokyo Metropolitan Institute for Neuroscience, Japan. ykubo@tmin.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Kubo
authors.forename: M
authors.initials: M
authors.lastname: Iizuka
mesh_terms: D000818:Animals; D001704:Biopolymers; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D019204:GTP-Binding Proteins / Q000378:metabolism*; D015640:Ion Channel Gating; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D015221:Potassium Channels / Q000737:chemistry / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D051381:Rats; D011976:Receptors, Muscarinic / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D014981:Xenopus
chemical_list: D001704:Biopolymers; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C092387:Kcnj5 protein, rat; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011976:Receptors, Muscarinic; D011993:Recombinant Fusion Proteins; D019204:GTP-Binding Proteins