A NOVEL INWARD RECTIFIER K+ CHANNEL WITH UNIQUE PORE PROPERTIES

We have cloned a novel K+-selective, inward rectifier channel that is widely expressed in brain but is especially abundant in the Purkinje c ell layer of the cerebellum and pyramidal cells of the hippocampus. It is also present in a wide array of tissues, including kidney and inte stine. The channel is only 38% identical to its closest relative, Kir1 .3 (Kir1-ATP-regulated inward rectifier K+ [ROMK] family) and displays none of the functional properties unique to the ROMK class. Kir7.1 ha s several unique features, including a very low estimated single chann el conductance (similar to 50 fS), low sensitivity to block by externa l Ba2+ and Cs+, and no dependence of its inward rectification properti es on the internal blocking particle Mg2+. The unusual pore properties of Kir7.1 seem to be explained by amino acids in the pore sequence th at differ from corresponding conserved residues in all other Kir chann el proteins. Replacement of one of these amino acids (Met-125) with th e Arg absolutely conserved in all other Kir channels dramatically incr eases its single channel conductance and Ba2+ sensitivity. This channe l would provide a steady background K+ current to help set the membran e potential in cells in which it is expressed. We propose that the nov el channel be assigned to a new Kir subfamily, Kir7.1.