Molecular determinants of ASIC1 modulation by divalent cations.
Sci Rep
; 14(1): 2320, 2024 01 28.
Article
em En
| MEDLINE
| ID: mdl-38282035
ABSTRACT
Acid-sensing ion channels (ASICs) are proton-gated cation channels widely expressed in the nervous system. ASIC gating is modulated by divalent cations as well as small molecules; however, the molecular determinants of gating modulation by divalent cations are not well understood. Previously, we identified two small molecules that bind to ASIC1a at a novel site in the acidic pocket and modulate ASIC1 gating in a manner broadly resembling divalent cations, raising the possibility that these small molecules may help to illuminate the molecular determinants of gating modulation by divalent cations. Here, we examined how these two groups of modulators might interact as well as mutational effects on ASIC1a gating and its modulation by divalent cations. Our results indicate that binding of divalent cations to an acidic pocket site plays a key role in gating modulation of the channel.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Prótons
/
Canais Iônicos Sensíveis a Ácido
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos