抄録
We have cloned five distinct types of inward-rectifying K+ 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. Xenopus oocytes injected with cRNAs for MB-IRKs and KAB-2 elicited background K+ currents, which showed the classical inward-rectifying K+ characteristics at the whole cell current level and were blocked by Ba2+ and Cs+ 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 Gβγ, ?? 35 pS; and KAB-2, either ?? 15 pS or ?? 30 pS with 150 mM [K+]o. Distribution of mRNAs for the clones was examined by Northern blot analysis and in situ 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+ 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.
