Functional modulation of voltage-dependent sodium channel expression by wild type and mutated C121W-ß1 subunit.
J Bioenerg Biomembr
; 45(4): 353-68, 2013 Aug.
Article
em En
| MEDLINE
| ID: mdl-23584539
ABSTRACT
Voltage dependent sodium channels are membrane proteins essential for cell excitability. They are composed by a pore-forming α-subunit, encoded in mammals by up to 9 different genes, and 4 different ancillary ß-subunits. The expression pattern of the α subunit isoforms confers the distinctive functional and pharmacological properties to different excitable tissues. ß subunits are important modulators of channel function and expression. Mutation C121W of the ß1-subunit causes an autosomal dominant epileptic syndrome without cardiac symptoms. The C121W mutation may act by a dominant-competition, modifying the expression of α-subunit proteins. To test this hypothesis, we transfected GH3 cells, from neuro-ectoderm origin, with wild-type or mutant ß1 subunits and compared them to native cells. To examine the tissue specificity of the C121W-ß1 mutation, we compared the effects of the mutation on neural cells with those of H9C2 cells of cardiac origin. We found that in GH3 cells the over-expression of the ß1 subunit augments the α subunit mRNA and protein levels, while in the H9C2 cells the enhanced level of ß1 subunit not only increases but also qualitatively modifies the sodium channel α isoform expression pattern. Interestingly, the introduction of the epileptogenic C121W-ß1 subunit does not alter the sodium channel isoform composition of GH3 cells, while produces additional changes in the α-subunit expression pattern of H9C2 cells. Electrophysiological measurements confirm these molecular results. The expression differences observed could be correlated to the tissue-specific regulatory action of the ß1 subunit and to the nervous system specificity of the C121W mutation. Our findings could be helpful for the comprehension of the molecular mechanism of generalised epileptic with febrile seizures plus in patients with identified ß1 subunit mutations.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Epilepsia
/
Canais de Sódio Disparados por Voltagem
/
Mutação
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Bioenerg Biomembr
Ano de publicação:
2013
Tipo de documento:
Article