A Novel Inward Rectifier K 1 Channel with Unique Pore Properties

be rapidly and efficiently depolarized, and between deWe have cloned a novel K-selective, inward rectifier polarizations only small amounts of K ions were lost. channel that is widely expressed in brain but is espeFor rapid repolarization, the largerconductance voltagecially abundant in the Purkinje cell layer of the cerebelsensitive Kv channels were brought into play. Several lum and pyramidal cells of the hippocampus. It is also Kir subfamilies (Kir1-ATP–regulated inward rectifier K present in a wide array of tissues, including kidney [ROMK], Kir3-G protein–gated inward rectifier K [GIRK], and intestine. The channel is only 38% identical to and Kir6-ATP–sensitive K channel [KATP]) are reguits closest relative, Kir1.3 (Kir1-ATP–regulated inward lated by second messengers, largely to alter the bursting rectifier K [ROMK] family) and displays none of the and pacing activity of cells like cardiac myocytes, neufunctional properties unique to the ROMK class. Kir7.1 rons, and secretory cells. Other subfamilies, such as has several unique features, including a very low estiIRKs, seem to be responsible for reliably setting the mated single channel conductance (z50 fS), low sensiresting membrane potential. In this paper, we describe tivity to block by external Ba21 and Cs, and no depena novel subfamily of Kirs, which is unique in all respects dence of its inward rectification properties on the within the Kir class of channels. internal blocking particleMg21. The unusual pore propAll K channel polypeptides share a homologous pore erties of Kir7.1 seem to be explained by amino acids region believed to form an integral part of the K-selecin the pore sequence that differ from corresponding tive pore (reviewed by Nichols and Lopatin, 1997). Repconserved residues in all other Kir channel proteins. resentative channels of this class include the ATP-sensiReplacement of one of these amino acids (Met-125) tive Kir1 (ROMK1; Ho et al., 1993), Kir2 (IRK1; Kubo et with the Arg absolutely conserved in all other Kir chanal., 1993a), the G protein–gated Kir3 channels (GIRK1; nels dramatically increases its single channel conducKubo et al., 1993b), Kir4 and Kir5 (Bond et al., 1994), tance and Ba21 sensitivity. This channel would provide and Kir6 (IKATP when combined with the sulfanylurea a steady background K current to help set the memreceptor; Inagaki et al., 1995a). Unlike the six-transmembrane potential in cells in which it is expressed. We brane-spanning class of outwardly rectifying K chanpropose that the novel channel be assigned to a new nels, Kir channels are weakly voltage dependent. ProbaKir subfamily, Kir7.1. bly the most interesting feature of Kir channels is that