The activation gate controls steady-state inactivation and recovery from inactivation in Shaker.


Journal

The Journal of general physiology
ISSN: 1540-7748
Titre abrégé: J Gen Physiol
Pays: United States
ID NLM: 2985110R

Informations de publication

Date de publication:
03 08 2020
Historique:
received: 14 02 2020
accepted: 18 04 2020
entrez: 23 5 2020
pubmed: 23 5 2020
medline: 3 9 2021
Statut: ppublish

Résumé

Despite major advances in the structure determination of ion channels, the sequence of molecular rearrangements at negative membrane potentials in voltage-gated potassium channels of the Shaker family remains unknown. Four major composite gating states are documented during the gating process: closed (C), open (O), open-inactivated (OI), and closed-inactivated (CI). Although many steps in the gating cycle have been clarified experimentally, the development of steady-state inactivation at negative membrane potentials and mandatory gating transitions for recovery from inactivation have not been elucidated. In this study, we exploit the biophysical properties of Shaker-IR mutants T449A/V474C and T449A/V476C to evaluate the status of the activation and inactivation gates during steady-state inactivation and upon locking the channel open with intracellular Cd2+. We conclude that at negative membrane potentials, the gating scheme of Shaker channels can be refined in two aspects. First, the most likely pathway for the development of steady-state inactivation is C→O→OI⇌CI. Second, the OI→CI transition is a prerequisite for recovery from inactivation. These findings are in accordance with the widely accepted view that tight coupling is present between the activation and C-type inactivation gates in Shaker and underscore the role of steady-state inactivation and recovery from inactivation as determinants of excitability.

Identifiants

pubmed: 32442242
pii: 151805
doi: 10.1085/jgp.202012591
pmc: PMC7398138
pii:
doi:

Substances chimiques

Shaker Superfamily of Potassium Channels 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : NIGMS NIH HHS
ID : R01 GM052302
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2020 Szanto et al.

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Auteurs

Tibor G Szanto (TG)

Division of Biophysics, Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

Florina Zakany (F)

Division of Biophysics, Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

Ferenc Papp (F)

Division of Biophysics, Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

Zoltan Varga (Z)

Division of Biophysics, Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

Carol J Deutsch (CJ)

Department of Physiology, University of Pennsylvania, Philadelphia, PA.

Gyorgy Panyi (G)

Division of Biophysics, Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

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