内向き整流性カリウムチャネルの分子多様性とその機能  [in Japanese] Molecular and functional heterogeneity of inward-rectifying potassium channels  [in Japanese]

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Abstract

We have cloned five distinct types of inward-rectifying K<SUP>+</SUP> channels with two putative transmembrane regions from mouse and rat brain cDNA libraries. We designated these novel clones as MB-IRK1, MB-IRK2, MB-IRK3, MB-GIRK1 and KAB-2. <I>Xenopus</I> oocytes injected with cRNAs for MB-IRKs and KAB-2 elicited background K<SUP>+</SUP> currents, which showed the classical inward-rectifying K<SUP>+</SUP> characteristics at the whole cell current level and were blocked by Ba<SUP>2+</SUP> and Cs<SUP>+</SUP> in a concentration- and voltage-dependent manner. The single channel recordings revealed that the unitary conductance of MB-IRKI was ?? 22 pS; MB-IRK2, ?? 35 pS; MB-IRK3, ?? 12 pS; MB-GIRK1 which was activated by G<SUB>βγ</SUB>, ?? 35 pS; and KAB-2, either ?? 15 pS or ?? 30 pS with 150 mM [K<SUP>+</SUP>]<I>o</I>. Distribution of mRNAs for the clones was examined by Northern blot analysis and in <I>situ</I> hybridization technique. MB-IRKI mRNA was detected strongly in forebrain, heart and skeletal muscle, and less in cerebellum, but not in kidney. MB-IRK2 mRNA was detected strongly in cerebellum and less in other previously described organs. MB-IRK3 mRNA was detected specifically in forebrain. MB-GIRK 1 mRNA was detected strongly in forebrain, cerebellum and heart, and less in skeletal muscle, but not in kidney. KAB-2 mRNA was detected strongly in forebrain and cerebellum, less in kidney, but not in heart or skeletal muscle. In situ hybridization showed mRNAs for the clones to be expressed in a variety of regions throughout the brain. These results indicate that the clones of inward-rectifying K<SUP>+</SUP> channels with two putative transmembrane regions may play heterogeneous functional roles in various organs and provide a tool for future development of novel therapeutic strategies of various diseases.

Journal

  • Folia Pharmacologica Japonica

    Folia Pharmacologica Japonica 106, 56-60, 1995-09-01

    The Japanese Pharmacological Society

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