ReviewChannels (Austin, Tex.)
Characterization of the gating brake in the I-II loop of CaV3 T-type calcium channels.
Review in Channels (Austin, Tex.). The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- CaHandbook of experimental pharmacology · 2023Article
- Structure, gating, and pharmacology of human CaNature communications · 2022Article
- Targeting T-type/CaV3.2 channels for chronic pain.Translational research : the journal of laboratory and clinical medicine · 2021Review
- Ion Channel Function and Electrical Excitability in the Zona Glomerulosa: A Network Perspective on Aldosterone Regulation.Annual review of physiology · 2021Review
- Role of individual S4 segments in gating of CaChannels (Austin, Tex.) · 2018Article
- Contribution of S4 segments and S4-S5 linkers to the low-voltage activation properties of T-type CaV3.3 channels.PloS one · 2018Article
- Calmodulin regulates CaThe Journal of biological chemistry · 2017Article
- Evolutionary insights into T-type CaThe Journal of general physiology · 2017Article
- Physiology and Evolution of Voltage-Gated Calcium Channels in Early Diverging Animal Phyla: Cnidaria, Placozoa, Porifera and Ctenophora.Frontiers in physiology · 2016Article
- T-type channels: release a brake, engage a gear.Channels (Austin, Tex.) · 2016Article
- Contrasting the roles of the I-II loop gating brake in CaV3.1 and CaV3.3 calcium channels.Pflugers Archiv : European journal of physiology · 2015Article
- Phosphorylation of the Cav3.2 T-type calcium channel directly regulates its gating properties.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- C-terminal modulatory domain controls coupling of voltage-sensing to pore opening in Cav1.3 L-type Ca(2+) channels.Biophysical journal · 2014Article
- Ins and outs of T-channel structure function.Pflugers Archiv : European journal of physiology · 2014Review
- Cav3 T-type channels: regulators for gating, membrane expression, and cation selectivity.Pflugers Archiv : European journal of physiology · 2014Review
- Trafficking and stability of voltage-gated calcium channels.Cellular and molecular life sciences : CMLS · 2012Review
- The voltage dependence of gating currents of the neuronal CA(v)3.3 channel is determined by the gating brake in the I-II loop.Pflugers Archiv : European journal of physiology · 2011Article
- A uniquely adaptable pore is consistent with NALCN being an ion sensor.Channels (Austin, Tex.)Article
Corrections and comments
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Authors and funding
1 author at 1 institution in 1 country.
Funding
Abstract
Our interest was drawn to the I-II loop of Cav3 channels for two reasons: one, transfer of the I-II loop from a high voltage-activated channel (Cav2.2) to a low voltage-activated channel (Cav3.1) unexpectedly produced an ultra-low voltage activated channel; and two, sequence variants of the I-II loop found in childhood absence epilepsy patients altered channel gating and increased surface expression of Cav3.2 channels. To determine the roles of this loop we have studied the structure of the loop and the biophysical consequences of altering its structure. Deletions localized the gating brake to the first 62 amino acids after IS6 in all three Cav3 channels, establishing the evolutionary conservation of this region and its function. Circular dichroism was performed on a purified fragment of the I-II loop from Cav3.2 to reveal a high α-helical content. De novo computer modeling predicted the gating brake formed a helix-loop-helix structure. This model was tested by replacing the helical regions with poly-proline-glycine (PGPGPG), which introduces kinks and flexibility. These mutations had profound effects on channel gating, shifting both steady-state activation and inactivation curves, as well as accelerating channel kinetics. Mutations designed to preserve the helical structure (poly-alanine, which forms α-helices) had more modest effects. Taken together, we conclude the second helix of the gating brake establishes important contacts with the gating machinery, thereby stabilizing a closed state of T-channels, and that this interaction is disrupted by depolarization, allowing the S6 segments to spread open and Ca (2+) ions to flow through.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.