Lipid-dependent gating of a voltage-gated potassium channel
Open accessAbstract
Recent studies hypothesized that phospholipids stabilize two voltage-sensing arginine residues of certain voltage-gated potassium channels in activated conformations. It remains unclear how lipids directly affect these channels. Here, by examining the conformations of the KvAP in different lipids, we showed that without voltage change, the voltage-sensor domains switched from the activated to the resting state when their surrounding lipids were changed from phospholipids to nonphospholipids. Such lipid-determined conformational change was coupled to the ion-conducting pore, suggesting that parallel to voltage gating, the channel is gated by its annular lipids. Our measurements recognized that the energetic cost of lipid-dependent gating approaches that of voltage gating, but kinetically it appears much slower. Our data support that a channel and its surrounding lipids together constitute a functional unit, and natural nonphospholipids such as cholesterol should exert strong effects on voltage-gated channels. Our first observation of lipid-dependent gating may have general implications to other membrane proteins. Lipid phosphodiesters affect the conformation of certain potassium channels, but the details of the lipid-channel interactions are unclear. Here, the KvAP channel is found to switch from an active to a resting state when the channels are transferred from a phospholipid membrane to a bilayer lacking phosphodiesters.
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A shift in the ratio of specific GPL subclasses can affect membrane properties such as its fluidity and curvature, which can further modulate neuronal excitability.
“In addition, a shift in the ratio of specific GPL subclasses can affect membrane properties such as its fluidity and curvature, 25 which can further modulate neuronal excitability.45,47,71”
From Large neutral amino acid levels tune perinatal neuronal excitability and survival (2023) · cites this paper as [45]
The Results section ('Cholesterol effect on KvAP as predicted by lipid gating'; page unavailable) reports that changing membrane lipid composition altered gating of the KvAP potassium channel. The Discussion (page unavailable) likewise proposes that lipids help determine whether voltage-gated channels open or close. The paper does not show that shifts among specific GPL subclasses change membrane fluidity or curvature, or that those changes modulate neuronal excitability; its experiments used a prokaryotic channel in artificial membranes. (LLM, conf=0.84)
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- Authors
- Zheng, H., Liu, W., Anderson, L. Y., & Jiang, Q.-X.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- University of Houston (US)
- Corresponding author
- Jiang, Qiu-Xing
- Venue
- Nature Communications
- Published
- 2011-03-22
- Volume
- 2
- Issue
- 1
- Pages
- 250-250
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC3072105
- OpenAlex
- W2107872165
- Cited by
- 106
- References
- 60
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 8 · 2023: 5 · 2022: 3 · 2021: 6 · 2020: 2 · 2019: 7 · 2018: 5 · 2017: 4 · 2016: 7 · 2015: 9 · 2014: 9 · 2013: 11 · 2012: 12
- FWCI
- 4.55
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- American Heart Association
- Yale University
- Brandeis University
- University of Texas Southwestern Medical Center
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM093271, R01GM088745)
- National Institute of Neurological Disorders and Stroke
- Eurostars
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- voltage-gated potassium channels, KvAP, voltage-sensing domain, arginine residues, phospholipids, cholesterol, channel conformational change
- MeSH terms
- Arginine, Cysteine, Kinetics, Membranes, Artificial, Models, Molecular, Molecular Conformation, Phospholipids, Recombinant Proteins, Ion Channel Gating, Gene Expression, Mutagenesis, Site-Directed, Protein Structure, Tertiary, Archaeal Proteins, Potassium Channels, Voltage-Gated, Aeropyrum
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