Leaky sodium channels from voltage sensor mutations in periodic paralysis, but not paramyotonia
نویسندگان
چکیده
منابع مشابه
Voltage-sensor movements describe slow inactivation of voltage-gated sodium channels II: A periodic paralysis mutation in NaV1.4 (L689I)
In skeletal muscle, slow inactivation (SI) of Na(V)1.4 voltage-gated sodium channels prevents spontaneous depolarization and fatigue. Inherited mutations in Na(V)1.4 that impair SI disrupt activity-induced regulation of channel availability and predispose patients to hyperkalemic periodic paralysis. In our companion paper in this issue (Silva and Goldstein. 2013. J. Gen. Physiol. http://dx.doi....
متن کاملIon permeation and block of the gating pore in the voltage sensor of NaV1.4 channels with hypokalemic periodic paralysis mutations
Hypokalemic periodic paralysis and normokalemic periodic paralysis are caused by mutations of the gating charge-carrying arginine residues in skeletal muscle Na(V)1.4 channels, which induce gating pore current through the mutant voltage sensor domains. Inward sodium currents through the gating pore of mutant R666G are only approximately 1% of central pore current, but substitution of guanidine ...
متن کاملVoltage-sensor sodium channel mutations cause hypokalemic periodic paralysis type 2 by enhanced inactivation and reduced current.
The pathomechanism of familial hypokalemic periodic paralysis (HypoPP) is a mystery, despite knowledge of the underlying dominant point mutations in the dihydropyridine receptor (DHPR) voltage sensor. In five HypoPP families without DHPR gene defects, we identified two mutations, Arg-672-->His and -->Gly, in the voltage sensor of domain 2 of a different protein: the skeletal muscle sodium chann...
متن کاملThe voltage sensor module in sodium channels.
The mechanism by which voltage-gated ion channels respond to changes in membrane polarization during action potential signaling in excitable cells has been the subject of research attention since the original description of voltage-dependent sodium and potassium flux in the squid giant axon. The cloning of ion channel genes and the identification of point mutations associated with channelopathy...
متن کاملOutward stabilization of the voltage sensor in domain II but not domain I speeds inactivation of voltage-gated sodium channels.
To determine the roles of the individual S4 segments in domains I and II to activation and inactivation kinetics of sodium current (INa) in NaV1.5, we used a tethered biotin and avidin approach after a site-directed cysteine substitution was made in the second outermost Arg in each S4 (DI-R2C and DII-R2C). We first determined the fraction of gating charge contributed by the individual S4's to m...
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ژورنال
عنوان ژورنال: Neurology
سال: 2011
ISSN: 0028-3878,1526-632X
DOI: 10.1212/wnl.0b013e318219fb57