Cloning of a Xenopus laevis inwardly rectifying K+ channel subunit that permits GIRK1 expression of IKACh currents in oocytes.
Xenopus oocytes injected with GIRK1 mRNA express inwardly rectifying K+ channels resembling IKACh. Yet IKACh, the atrial G protein-regulated ion channel, is a heteromultimer of GIRK1 and CIR. Reasoning that an oocyte protein might be substituting for CIR, we cloned XIR, a CIR homolog endogenously expressed by Xenopus oocytes. Coinjecting XIR and GIRK1 mRNAs produced large, inwardly rectifying K+ currents responsive to m2-muscarinic receptor stimulation. The m2-stimulated currents of oocytes expressing GIRK1 alone decreased 80% after injecting antisense oligonucleotides specific to the 5' untranslated region of XIR, but GIRK1/CIR currents were unaffected. Thus, GIRK1 without XIR or CIR only ineffectively produces currents in oocytes. This result suggests that GIRK1 does not form native homomultimeric channels.
Hedin
K E
KE
Department of Pharmacology, Mayo Foundation, Rochester, Minnesota 55905, USA.
Lim
N F
NF
Clapham
D E
DE
D000109:Acetylcholine / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D004553:Electric Conductivity; D005260:Female; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D009865:Oocytes / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D017385:Sequence Homology; D014982:Xenopus laevis / Q000378:metabolism*
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D016376:Oligonucleotides, Antisense; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D000109:Acetylcholine