Cold induces shifts of voltage dependence in mutant SCN4A, causing hypokalemic periodic paralysis.
Neurology
; 61(7): 914-8, 2003 Oct 14.
Article
em En
| MEDLINE
| ID: mdl-14557559
ABSTRACT
BACKGROUND:
The authors reported a mutation, P1158S, of the human skeletal muscle sodium channel gene (SCN4A) in a family with cold-induced hypokalemic periodic paralysis (hypoKPP) and myotonia.OBJECTIVE:
To identify mechanisms of temperature dependency in this channelopathy.METHODS:
Using the amphotericin B perforated patch clamp method, sodium currents were recorded at 22 and 32 degrees C from the wild-type (WT) and P1158S mutant SCN4A expressed in tsA201 cells. Computer simulation was performed, incorporating the gating parameters of the P1158S mutant SCN4A.RESULTS:
P1158S mutant SCN4A exhibited hyperpolarizing shifts in voltage dependence of both activation and inactivation curves at a cold temperature and a slower rate of inactivation than the WT. Computer simulation reproduced the abnormal skeletal muscle electrical activities of both paralysis at a low potassium concentration in the cold and myotonia at a normal potassium concentration.CONCLUSIONS:
Both paralysis and myotonia are attributable to the biophysical properties of the SCN4A mutation associated with hypoKPP. This is the first report of an SCN4A mutation that exhibits temperature-dependent shifts of voltage dependence in sodium channel gating.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sódio
/
Canais de Sódio
/
Temperatura Baixa
/
Paralisia Periódica Hipopotassêmica
Limite:
Humans
Idioma:
En
Revista:
Neurology
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
Japão