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Conformational changes associated with ion permeation in L-type calcium channels
D Pietrobon1, B Prod'hom, P Hess
1Department of Cellular and Molecular Physiology, Harvard Medical School, Boston, Massachusetts 02115.
Nature
|May 26, 1988
Summary
Permeant cations binding to L-type calcium channels induce conformational changes. This alters the protonation state of the channel surface, impacting ion permeation mechanisms.
Area of Science:
- Biophysics
- Molecular Biology
- Ion Channel Physiology
Background:
- Ion-mediated signaling relies on protein conformational changes.
- Conformational changes in ion channels due to permeant ions are understudied.
- L-type calcium channels are crucial for cellular signaling.
Purpose of the Study:
- To investigate conformational changes in L-type calcium channels induced by permeant cations.
- To understand the functional consequences of ion binding within the channel.
- To explore the relationship between ion binding and channel surface protonation.
Main Methods:
- Studied dihydropyridine (DHP)-sensitive L-type Ca2+ channels.
- Investigated cation binding to intra-channel sites.
- Analyzed conformational changes and their effect on external surface protonation.
- Correlated protonated state lifetime with intra-channel binding site occupancy.
Main Results:
- Permeant cation binding induces a conformational change in L-type Ca2+ channels.
- This conformational change destabilizes the protonated state of an external channel group.
- Apparent pK value shifts by over 2 pH units.
- Protonated state lifetime correlates with cation binding site occupancy.
Conclusions:
- Permeant ions induce significant conformational changes in channel proteins.
- These changes directly affect channel surface properties and protonation states.
- Findings necessitate refined models of ion permeation mechanisms in channels.