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Sodium channel inactivation defects are associated with acetazolamide‐exacerbated hypokalemic periodic paralysis
Author(s) -
Bendahhou Saïd,
Cummins Theodore R.,
Griggs Robert C.,
Fu YingHui,
Ptáček Louis J.
Publication year - 2001
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.1144
Subject(s) - hypokalemic periodic paralysis , sodium channel , acetazolamide , mutation , periodic paralysis , mutant , paralysis , endocrinology , medicine , chemistry , biology , sodium , neuroscience , gene , hypokalemia , biochemistry , surgery , organic chemistry
Abstract A novel mutation in a family with hypokalemic periodic paralysis is described. The mutation R672S is located in the voltage sensor segment S4 of domain II in the SCN4A gene encoding the human skeletal muscle voltage‐gated sodium channel. Functional expression of the R672S channels in human embryonic kidney 293 cells revealed a small but significant hyperpolarizing shift in the steady‐state fast inactivation, and a dramatic enhancement in channel slow inactivation. These two defects are mainly due to a slow recovery of the mutant channels from fast and/or slow inactivation. Our data may help explain the mechanism underlying hypokalemic periodic paralysis and the patient's worsening from acetazolamide.