CLONING OF A XENOPUS-LAEVIS INWARDLY RECTIFYING K-KACH CURRENTS IN OOCYTES( CHANNEL SUBUNIT THAT PERMITS GIRK1 EXPRESSION OF I)

Xenopus oocytes injected with GIRK1 mRNA express inwardly rectifying K + channels resembling I-KACh. Yet I-KACh, the atrial G protein-regulat ed ion channel, is a heteromultimer of GIRK1 and CIR. Reasoning that a n oocyte protein might be substituting for CIR, we cloned XIR, a CIR h omolog 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 G IRK1/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.