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The protein IsK is a dual activator of K+ and CI channels

Abstract

THE protein IsK (Mr 14,500) is present in epithelial cells1, heart2,3, uterus4 and lymphocytes5 and induces slowly activating K+ currents when expressed in Xenopus oocytes1. The finding that mutations of its single transmembrane segment altered channel gating6 or selectivity7 has suggested that IsK is a channel-forming protein. But IsK does nof exhibit the K+ channel hallmarks8 (a conserved K+ selective pore (H5) flanked by either six9–11 or two12,13 membrane-spanning regions). Here we report that IsK expression in Xenopus oocytes also induces a Cl selective current very similar to the Cl current produced by phospholemman expression14 and with biophysical, pharmacological and regulation characteristics very different from those of the IsK-induced K+ channel activity. IsK mutagenesis identifies amino- and carboxy-terminal domains as critical for the induction of Cl and K+ channel activities, respectively. Our data lead to a model in which the IsK protein (now called IsK, Cl) acts as a potent activator of endogenous and otherwise silent K+ or Cl channels.

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Attali, B., Guillemare, E., Lesage, F. et al. The protein IsK is a dual activator of K+ and CI channels. Nature 365, 850–852 (1993). https://doi.org/10.1038/365850a0

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