Simulation of Gating Currents of the Shaker K Channel Using a Brownian Model of the Voltage Sensor.
Biophys J
; 117(10): 2005-2019, 2019 11 19.
Article
em En
| MEDLINE
| ID: mdl-31653450
ABSTRACT
The physical mechanism underlying the voltage-dependent gating of K channels is usually addressed theoretically using molecular dynamics simulations. However, besides being computationally very expensive, this approach is presently unable to fully predict the behavior of fundamental variables of channel gating such as the macroscopic gating current, and hence, it is presently unable to validate the model. To fill this gap, here we propose a voltage-gating model that treats the S4 segment as a Brownian particle moving through a gating channel pore and adjacent internal and external vestibules. In our model, charges on the S4 segment are screened by charged residues localized on neighboring segments of the channel protein and by ions present in the vestibules, whose dynamics are assessed using a flux conservation equation. The electrostatic voltage spatial profile is consistently assessed by applying the Poisson equation to all the charges present in the system. The treatment of the S4 segment as a Brownian particle allows description of the dynamics of a single S4 segment using the Langevin stochastic differential equation or the behavior of a population of S4 segments-useful for assessing the macroscopic gating current-using the Fokker-Planck equation. The proposed model confirms the gating charge transfer hypothesis with the movement of the S4 segment among five different stable positions where the gating charges interact in succession with the negatively charged residues on the channel protein. This behavior produces macroscopic gating currents quite similar to those experimentally found.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Simulação por Computador
/
Ativação do Canal Iônico
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Superfamília Shaker de Canais de Potássio
/
Modelos Biológicos
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Biophys J
Ano de publicação:
2019
Tipo de documento:
Article