A novel biophysical model on calcium and voltage dual dependent gating of calcium-activated chloride channel.
J Theor Biol
; 355: 229-35, 2014 Aug 21.
Article
em En
| MEDLINE
| ID: mdl-24727189
ABSTRACT
Ca(2+)-activated Cl(-) channels (CaCCs) are anion-selective channels and involved in physiological processes such as electrolyte/fluid secretion, smooth muscle excitability, and olfactory perception which critically depend on the Ca(2+) and voltage dual-dependent gating of channels. However, how the Ca(2+) and voltage regulate the gating of CaCCs still unclear. In this work, the authors constructed a biophysical model to illustrate the dual-dependent gating of CaCCs. For validation, we applied our model on both native CaCCs and exogenous TMEM16A which is thought to be the molecular basis of CaCCs. Our data show that the native CaCCs may share universal gating mechanism. We confirmed the assumption that by binding with the channel, Ca(2+) decreases the energy-barrier to open the channel, but not changes the voltage-sensitivity. For TMEM16A, our model indicates that the exogenous channels show different Ca(2+) dependent gating mechanism from the native ones. These results advance the understanding of intracellular Ca(2+) and membrane potential regulation in CaCCs, and shed new light on its function in aspect of physiology and pharmacology.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ativação do Canal Iônico
/
Cálcio
/
Canais de Cloreto
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Modelos Biológicos
/
Proteínas de Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Theor Biol
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
China