Sodium channel mutations in paramyotonia congenita uncouple inactivation from activation.
Neuron
; 12(2): 281-94, 1994 Feb.
Article
em En
| MEDLINE
| ID: mdl-8110459
ABSTRACT
Mutations in the adult human skeletal muscle Na+ channel alpha subunit cause the disease paramyotonia congenita. Two paramyotonia congenita mutations, R1448H and R1448C, substitute histidine and cysteine for arginine in the S4 segment of domain 4. These mutations, expressed in a cell line, have only small effects on the activation of Na+ currents, but mutant channels inactivate more slowly with less voltage dependence than wild-type channels and exhibit an enhanced rate of recovery from inactivation. Increase of extracellular pH made the rate of inactivation of R1448H similar to that of R1448C, suggesting that this residue has an extracellular location and that its charge is important for normal inactivation. Analysis of single-channel data reveals that mutant channels inactivate normally from closed states, but poorly from the open state. The data suggest a critical role for the S4 helix of domain 4 in coupling between activation and inactivation.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Canais de Sódio
/
Mutação
/
Miotonia Congênita
Limite:
Humans
Idioma:
En
Revista:
Neuron
Assunto da revista:
NEUROLOGIA
Ano de publicação:
1994
Tipo de documento:
Article