Functional consequences of a Na+ channel mutation causing hyperkalemic periodic paralysis.
Neuron
; 10(4): 667-78, 1993 Apr.
Article
em En
| MEDLINE
| ID: mdl-8386527
ABSTRACT
Hyperkalemic periodic paralysis (HYPP), one of several inheritable myotonic diseases, results from genetic defects in the human skeletal muscle Na+ channel. In some pedigrees, HYPP is correlated with a single base pair substitution resulting in a Met replacing Thr704 in the fifth transmembrane segment of the second domain. This region is totally conserved between the human and rat channels. We have introduced the human mutation into the corresponding region of the rat muscle Na+ channel cDNA and expressed it in human embryonic kidney 293 cells. Patch-clamp recordings show that this mutation shifts the voltage dependence of activation by 10-15 mV in the negative direction. The shift results in a persistent Na+ current that activates near -70 mV; this phenomenon could underlie the abnormal muscle activity observed in patients with HYPP.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Paralisia
/
Periodicidade
/
Canais de Sódio
/
Hiperpotassemia
/
Mutação
Limite:
Humans
Idioma:
En
Ano de publicação:
1993
Tipo de documento:
Article