THE EPITHELIAL INWARD RECTIFIER CHANNEL KIR7.1 DISPLAYS UNUSUAL K+ PERMEATION PROPERTIES

Rat and human cDNAs were isolated that both encoded a 360 amino acid p olypeptide with a tertiary structure typical of inwardly rectifying K channel (Kir) subunits. The new proteins, termed Kir7.1, were <37% id entical to other Kir subunits and showed various unique residues at co nserved sites, particularly near the pore region. High levels of Kir7. 1 transcripts were detected in rat brain, lung, kidney, and testis. In situ hybridization of rat brain sections demonstrated that Kir7.1 mRN A was absent from neurons and glia but strongly expressed in the secre tory epithelial cells of the choroid plexus (as confirmed by in situ p atch-clamp measurements). In cRNA-injected Xenopus oocytes Kir7.1 gene rated macroscopic Kir currents that showed a very shallow dependence o n external K+ ([K+](e)), which is in marked contrast to all other Kir channels. At a holding potential of -100 mV, the inward current throug h Kir7.1 averaged -3.8 +/- 1.04 mu A with 2 mM [K+](e) and -4.82 +/- 1 .87 mu A with 96 mM [K+](e). Kir7.1 has a methionine at position 125 i n the pore region where other Kir channels have an arginine. When this residue was replaced by the conserved arginine in mutant Kir7.1 chann els, the pronounced dependence of K+ permeability on [K+](e), characte ristic for other Kir channels, was restored and the Ba2+ sensitivity w as increased by a factor of similar to 25 (K-i = 27 mu M). These findi ngs support the important role of this site in the regulation of K+ pe rmeability in Kir channels by extracellular cations.