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Gating of inwardly rectifying K+ channels localized to a single negatively charged residue

Nature volume 371, pages 246–249 (1994)Cite this article

Abstract

INWARDLY rectifying K+ channels (IRKs) conduct current preferentially in the inward direction. This inward rectification has two components: voltage-dependent blockade by intracellular Mg2+(Mgi2+)l–7 and intrinsic gating8,9. Two members of this channel family, IRK1 (ref. 10) and ROMK1 (ref. 11), differ markedly in affinity for Mgi2+(ref. 12). We found that IRK1 and ROMK1 differ in voltage-dependent gating and searched for the gating structure by large-scale and site-directed mutagenesis. We found that a single amino-acid change within the putative transmembrane domain M2, aspartate (D) in IRK1 to the corresponding asparagine (N) in ROMK1, controls the gating phenotype. Mutation D172N in IRK1 produced ROMKl-like gating whereas the reverse mutation in ROMK1—N17ID—produced IRKl-like gating. Thus, a single negatively charged residue seems to be a crucial determinant of gating.

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Authors and Affiliations

  1. Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, 77030, USA

    Barbara A. Wible, Maurizio Taglialatela, Eckhard Ficker & Arthur M. Brown

  2. Department of Human Communication Sciences, Section of Pharmacology, 2nd School of Medicine, University of Naples 'Federico II', 5 via S. Pansini, 80121, Naples, Italy

    Maurizio Taglialatela

Authors
  1. Barbara A. Wible
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  2. Maurizio Taglialatela
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  3. Eckhard Ficker
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  4. Arthur M. Brown
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Wible, B., Taglialatela, M., Ficker, E. et al. Gating of inwardly rectifying K+ channels localized to a single negatively charged residue. Nature 371, 246–249 (1994). https://doi.org/10.1038/371246a0

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