Activation gating in HCN2 channels.
PLoS Comput Biol
; 14(3): e1006045, 2018 03.
Article
em En
| MEDLINE
| ID: mdl-29565972
ABSTRACT
Hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels control electrical rhythmicity in specialized brain and heart cells. We quantitatively analysed voltage-dependent activation of homotetrameric HCN2 channels and its modulation by the second messenger cAMP using global fits of hidden Markovian models to complex experimental data. We show that voltage-dependent activation is essentially governed by two separable voltage-dependent steps followed by voltage-independent opening of the pore. According to this model analysis, the binding of cAMP to the channels exerts multiple effects on the voltage-dependent gating It stabilizes the open pore, reduces the total gating charge from ~8 to ~5, makes an additional closed state outside the activation pathway accessible and strongly accelerates the ON-gating but not the OFF-gating. Furthermore, the open channel has a much slower computed OFF-gating current than the closed channel, in both the absence and presence of cAMP. Together, these results provide detailed new insight into the voltage- and cAMP-induced activation gating of HCN channels.
Texto completo:
1
Temas:
ECOS
/
Financiamentos_gastos
Bases de dados:
MEDLINE
Assunto principal:
Ativação do Canal Iônico
/
Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização
Tipo de estudo:
Health_economic_evaluation
Limite:
Animals
Idioma:
En
Revista:
PLoS Comput Biol
Assunto da revista:
BIOLOGIA
/
INFORMATICA MEDICA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Alemanha