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

Author Ryan, Devon P. Google Scholar
Dias-da-Silva, Magnus Régios Autor UNIFESP Google Scholar
Soong, Tuck Wah Google Scholar
Fontaine, Bertrand Google Scholar
Donaldson, Matt R. Google Scholar
Kung, Annie W. C. Google Scholar
Jongjaroenprasert, Wallaya Google Scholar
Liang, Mui Cheng Google Scholar
Khoo, Daphne H. C. Google Scholar
Cheah, Jin Seng Google Scholar
Ho, Su Chin Google Scholar
Bernstein, Harold S. Google Scholar
Maciel, Rui Monteiro de Barros Autor UNIFESP Google Scholar
Brown, Robert H. Google Scholar
Ptacek, Louis J. Google Scholar
Institution Univ Calif San Francisco
Natl Inst Neurosci
Univ Paris 06
Grp Hosp Pitie Salpetriere
Univ Hong Kong
Mahidol Univ
Natl Univ Singapore
Singapore Gen Hosp
Universidade Federal de São Paulo (UNIFESP)
Massachusetts Gen Hosp
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.
Language English
Sponsor Muscular Dystrophy Association
National Institutes of Health
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
C.B. Day Foundation
Grant number National Institutes of Health: U54 RR19481
CAPES: 2284/01-4
FAPESP: 2000/03442-4
FAPESP: 1999/03688-4
Date 2010-01-08
Published in Cell. Cambridge: Cell Press, v. 140, n. 1, p. 88-98, 2010.
ISSN 0092-8674 (Sherpa/Romeo, impact factor)
Publisher Cell Press
Extent 88-98
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000273391900017

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