Enhancement effects of martentoxin on glioma BK channel and BK channel (α+ß1) subtypes.
PLoS One
; 6(3): e15896, 2011 Mar 18.
Article
em En
| MEDLINE
| ID: mdl-21445248
ABSTRACT
BACKGROUND:
BK channels are usually activated by membrane depolarization and cytoplasmic Ca(2+). Especially,the activity of BK channel (α+ß4) can be modulated by martentoxin, a 37 residues peptide, with Ca(2+)-dependent manner. gBK channel (glioma BK channel) and BK channel (α+ß1) possessed higher Ca(2+) sensitivity than other known BK channel subtypes. METHODOLOGY AND PRINCIPALFINDINGS:
The present study investigated the modulatory characteristics of martentoxin on these two BK channel subtypes by electrophysiological recordings, cell proliferation and Ca(2+) imaging. In the presence of cytoplasmic Ca(2+), martentoxin could enhance the activities of both gBK and BK channel (α+ß1) subtypes in dose-dependent manner with EC(50) of 46.7 nM and 495 nM respectively, while not shift the steady-state activation of these channels. The enhancement ratio of martentoxin on gBK and BK channel (α+ß1) was unrelated to the quantitative change of cytoplasmic Ca(2+) concentrations though the interaction between martentoxin and BK channel (α+ß1) was accelerated under higher cytoplasmic Ca(2+). The selective BK pore blocker iberiotoxin could fully abolish the enhancement of these two BK subtypes induced by martentoxin, suggesting that the auxiliary ß subunit might contribute to the docking for martentoxin. However, in the absence of cytoplasmic Ca(2+), the activity of gBK channel would be surprisingly inhibited by martentoxin while BK channel (α+ß1) couldn't be affected by the toxin. CONCLUSIONS ANDSIGNIFICANCE:
Thus, the results shown here provide the novel evidence that martentoxin could increase the two Ca(2+)-hypersensitive BK channel subtypes activities in a new manner and indicate that ß subunit of these BK channels plays a vital role in this enhancement by martentoxin.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
/
Tipos_de_cancer
/
Outros_tipos
Base de dados:
MEDLINE
Assunto principal:
Venenos de Escorpião
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Neoplasias Encefálicas
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Canais de Potássio Ativados por Cálcio de Condutância Alta
/
Glioma
Limite:
Humans
Idioma:
En
Revista:
PLoS One
Assunto da revista:
CIENCIA
/
MEDICINA
Ano de publicação:
2011
Tipo de documento:
Article