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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acetazolamide / adverse effects*
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Action Potentials / drug effects
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Action Potentials / physiology
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Adolescent
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Adult
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Carbonic Anhydrase Inhibitors / adverse effects*
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Cell Line
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Female
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Humans
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Hypokalemic Periodic Paralysis / genetics
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Hypokalemic Periodic Paralysis / metabolism*
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Hypokalemic Periodic Paralysis / physiopathology
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Male
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Middle Aged
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Muscle, Skeletal / drug effects
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Muscle, Skeletal / physiology
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Mutation / genetics*
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Pedigree
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Sodium Channel Blockers*
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Sodium Channels / genetics*
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Sodium Channels / metabolism
Substances
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Carbonic Anhydrase Inhibitors
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Sodium Channel Blockers
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Sodium Channels
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Acetazolamide