2. Academic Validation
  3. Mutations in potassium channel Kir2.6 cause susceptibility to thyrotoxic hypokalemic periodic paralysis

Mutations in potassium channel Kir2.6 cause susceptibility to thyrotoxic hypokalemic periodic paralysis

  • Cell. 2010 Jan 8;140(1):88-98. doi: 10.1016/j.cell.2009.12.024.
Devon P Ryan 1,  Magnus R Dias da Silva,  Tuck Wah Soong,  Bertrand Fontaine,  Matt R Donaldson,  Annie W C Kung,  Wallaya Jongjaroenprasert,  Mui Cheng Liang,  Daphne H C Khoo,  Jin Seng Cheah,  Su Chin Ho,  Harold S Bernstein,  Rui M B Maciel,  Robert H Brown Jr,  Louis J Ptácek
Affiliations

Affiliation

  • 1 Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA, 94158, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA, 94158, USA.
PMID: 20074522 DOI: 10.1016/j.cell.2009.12.024
Abstract

Thyrotoxic hypokalemic periodic paralysis (TPP) is characterized by acute attacks of weakness, hypokalemia, and thyrotoxicosis of various etiologies. These transient attacks resemble those of patients with familial hypokalemic periodic paralysis (hypoKPP) and resolve with treatment of the underlying hyperthyroidism. Because of the phenotypic similarity of these conditions, we hypothesized that TPP might also be a channelopathy. While Sequencing candidate genes, we identified a previously unreported gene (not present in human sequence databases) that encodes an inwardly rectifying potassium (Kir) channel, Kir2.6. This channel, nearly identical to Kir2.2, is expressed in skeletal muscle and is transcriptionally regulated by thyroid hormone. Expression of Kir2.6 in mammalian cells revealed normal Kir currents in whole-cell and single-channel recordings. Kir2.6 mutations were present in up to 33% of the unrelated TPP patients in our collection. Some of these mutations clearly alter a variety of Kir2.6 properties, all altering muscle membrane excitability leading to paralysis.

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