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The Journal of Neuroscience, November 1, 1998, 18(21):8625-8636

The Epithelial Inward Rectifier Channel Kir7.1 Displays Unusual K⁺ Permeation Properties

Frank Döring¹, Christian Derst³, Erhard Wischmeyer¹, Christine Karschin¹, Ralf Schneggenburger², Jürgen Daut³, and Andreas Karschin¹

¹ Molecular Neurobiology of Signal Transduction and ² Department of Membrane Biophysics, Max-Planck-Institute for Biophysical Chemistry, D-37070 Göttingen, Germany, and ³ Institute for Normal and Pathological Physiology, University of Marburg, D-35037 Marburg, Germany

Rat and human cDNAs were isolated that both encoded a 360 amino acid polypeptide with a tertiary structure typical of inwardly rectifying K⁺ channel (Kir) subunits. The new proteins, termed Kir7.1, were <37% identical to other Kir subunits and showed various unique residues at conserved 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 mRNA was absent from neurons and glia but strongly expressed in the secretory epithelial cells of the choroid plexus (as confirmed by in situ patch-clamp measurements). In cRNA-injected Xenopus oocytes Kir7.1 generated macroscopic Kir currents that showed a very shallow dependence on external K⁺ ([K⁺]_e), which is in marked contrast to all other Kir channels. At a holding potential of 100 mV, the inward current through Kir7.1 averaged 3.8 ± 1.04 µA with 2 mM [K⁺]_e and 4.82 ± 1.87 µA with 96 mM [K⁺]_e. Kir7.1 has a methionine at position 125 in the pore region where other Kir channels have an arginine. When this residue was replaced by the conserved arginine in mutant Kir7.1 channels, the pronounced dependence of K⁺ permeability on [K⁺]_e, characteristic for other Kir channels, was restored and the Ba²⁺ sensitivity was increased by a factor of ~25 (K_i = 27 µM). These findings support the important role of this site in the regulation of K⁺ permeability in Kir channels by extracellular cations.

Key words: inwardly rectifying; choroid plexus; Kir7.1; pore loop; in situ hybridization; Ba²⁺ block

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Copyright © 1998 Society for Neuroscience  0270-6474/98/18218625-12$05.00/0

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