Heteromeric channel formation and Ca(2+)-free media reduce the toxic effect of the weaver Kir 3.2 allele.
FEBS Lett
; 390(3): 253-7, 1996 Jul 29.
Article
em En
| MEDLINE
| ID: mdl-8706871
ABSTRACT
Weaver mice have a severe hypoplasia of the cerebellum with an almost complete loss of the midline granule cells. Recent genetic studies of weaver mice have identified a mutation resulting in an amino acid substitution (G156S) in the pore of the inwardly rectifying potassium channel subunit Kir 3.2. When expressed in Xenopus oocytes the weaver mutation alters channel selectivity from a potassium-selective to a nonspecific cation-selective pore. In this study we confirm by cell-attached patch-clamp recording that the mutation produces a non-selective cation channel. We also demonstrate that the cell death induced by weaver expression may be prevented by elimination of calcium from the extracellular solution as well as by coexpression with the wild-type Kir 3.2 allele, or other members of the Kir 3.0 subfamily. These results suggest that the weaver defect in Kir 3.2 may cause cerebellar cell death by cell swelling and calcium overload. Cells which express the weaver subunit, but which normally survive, may do so because of heteromeric subunit assembly with wild-type subunits of the Kir 3.0 subfamily.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Canais de Potássio
/
Sobrevivência Celular
/
Cálcio
/
Canais de Potássio Corretores do Fluxo de Internalização
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
FEBS Lett
Ano de publicação:
1996
Tipo de documento:
Article
País de afiliação:
Estados Unidos