CLONING AND CHARACTERIZATION OF A NOVEL HUMAN INWARDLY RECTIFYING POTASSIUM CHANNEL PREDOMINANTLY EXPRESSED IN SMALL-INTESTINE

A new member of the two transmembrane domain potassium (K+) channel fa mily was identified and isolated from a human brain cDNA library. The cDNA clone contains an open reading frame which encodes a 360 amino ac id sequence with a characteristic P domain flanked by two hydrophobic regions representing the membrane spanning segments, The closest homol ogue of this gene product is the inwardly rectifying potassium channel subunit, Kir1.2 (identity approximately 42%), Northern blot analysis of human tissues with a selective cDNA probe for this new K+ subunit s howed a single major transcript of 3.4 kb predominantly expressed at h igh levels in small intestine,,vith lower levels in stomach, kidney an d brain. The main regions of expression in the central nervous system were medulla, hippocampus and corpus callosum, cRNA-injected oocytes a nd transiently transfected HEK293 cells expressed a K+ conductance whi ch displays an inward rectification. This conductance is blocked by ce sium and barium but is insensitive to tolbutamide and diazoxide even u pon co-transfection of this novel subunit with the plasmid encoding th e sulfonylurea receptor SUR1. Taken together, these results demonstrat e that we have isolated and characterized a novel K+ channel subunit b elonging to the inwardly rectifying K+ (Kir) channel family to which, upon homology classification, we have given the nomenclature Kir7.1. ( C) 1998 Federation of European Biochemical Societies.