A model of the interaction between N-type and C-type inactivation in Kv1.4 channels.
Biophys J
; 100(1): 11-21, 2011 Jan 05.
Article
em En
| MEDLINE
| ID: mdl-21190652
ABSTRACT
Kv1.4 channels are Shaker-related voltage-gated potassium channels with two distinct inactivation mechanisms. Fast N-type inactivation operates by a ball-and-chain mechanism. Slower C-type inactivation is not so well defined, but involves intracellular and extracellular conformational changes of the channel. We studied the interaction between inactivation mechanisms using two-electrode voltage-clamp of Kv1.4 and Kv1.4ΔN (amino acids 2-146 deleted to remove N-type inactivation) heterologously expressed in Xenopus oocytes. We manipulated C-type inactivation by introducing a lysine-tyrosine point mutation (K532Y, equivalent to Shaker T449Y) that diminishes C-type inactivation. We used experimental data to develop a comprehensive computer model of Kv1.4 channels to determine the interaction between activation and N- and C-type inactivation mechanisms needed to replicate the experimental data. C-type inactivation began at lower voltage preactivated states, whereas N-type inactivation was coupled directly to the open state. A model with distinct N- and C-type inactivated states was not able to reproduce experimental data, and direct transitions between N- and C-type inactivated states were required, i.e., there is coupling between N- and C-type inactivated states. C-type inactivation is the rate-limiting step determining recovery from inactivation, so understanding C-type inactivation, and how it is coupled to N-type inactivation, is critical in understanding how channels act to repetitive stimulation.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Ativação do Canal Iônico
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Canal de Potássio Kv1.4
/
Modelos Biológicos
Limite:
Animals
Idioma:
En
Revista:
Biophys J
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos