Back to Search
Start Over
The activation gate controls steady-state inactivation and recovery from inactivation in Shaker.
- Source :
-
The Journal of general physiology [J Gen Physiol] 2020 Aug 03; Vol. 152 (8). - Publication Year :
- 2020
-
Abstract
- 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.<br /> (© 2020 Szanto et al.)
Details
- Language :
- English
- ISSN :
- 1540-7748
- Volume :
- 152
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- The Journal of general physiology
- Publication Type :
- Academic Journal
- Accession number :
- 32442242
- Full Text :
- https://doi.org/10.1085/jgp.202012591