ArticleProceedings of the National Academy of Sciences of the United States of America2014
Functional heterogeneity of the four voltage sensors of a human L-type calcium channel.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed.
- Voltage-sensing domains: structural and functional diversity.European biophysics journal : EBJ · 2026Review
- Allosteric interactions between RyR channels justify intracellular Ca2+ release of skeletal muscle in quantitative detail.The Journal of general physiology · 2026Article
- The four voltage-sensing domains of T-type calcium channels activate near the resting membrane potential.Nature communications · 2026Article
- A Historical Outline of Fluorescence Spectroscopy in Ion Channel Research.Advances in experimental medicine and biology · 2026Review
- The molecular transition that confers voltage dependence to muscle contraction.Nature communications · 2025Article
- A rich conformational palette underlies human CaNature communications · 2025Article
- Voltage sensors.Molecular pharmacology · 2025Review
- Genetic Code Expansion for Mechanistic Studies in Ion Channels: An (Un)natural Union of Chemistry and Biology.Chemical reviews · 2024Review
- Voltage-dependent G-protein regulation of CaScience advances · 2024Article
- CaNature communications · 2024Article
- Advances in CaChannels (Austin, Tex.) · 2023Review
- Fifty years of gating currents and channel gating.The Journal of general physiology · 2023Review
- Molecular insights into the gating mechanisms of voltage-gated calcium channel CaNature communications · 2023Article
- Functional Characterization of Four Known Cav2.1 Variants Associated with Neurodevelopmental Disorders.Membranes · 2023Article
- Complex effects on CaScientific reports · 2022Article
- Structure, gating, and pharmacology of human CaNature communications · 2022Article
- Article
- The distinct role of the four voltage sensors of the skeletal CaV1.1 channel in voltage-dependent activation.The Journal of general physiology · 2021Article
- Ion-pair interactions between voltage-sensing domain IV and pore domain I regulate CaBiophysical journal · 2021Article
- Voltage sensor movements of CaProceedings of the National Academy of Sciences of the United States of America · 2021Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Excitation-evoked Ca(2+) influx is the fastest and most ubiquitous chemical trigger for cellular processes, including neurotransmitter release, muscle contraction, and gene expression. The voltage dependence and timing of Ca(2+) entry are thought to be functions of voltage-gated calcium (CaV) channels composed of a central pore regulated by four nonidentical voltage-sensing domains (VSDs I-IV). Currently, the individual voltage dependence and the contribution to pore opening of each VSD remain largely unknown. Using an optical approach (voltage-clamp fluorometry) to track the movement of the individual voltage sensors, we discovered that the four VSDs of CaV1.2 channels undergo voltage-evoked conformational rearrangements, each exhibiting distinct voltage- and time-dependent properties over a wide range of potentials and kinetics. The voltage dependence and fast kinetic components in the activation of VSDs II and III were compatible with the ionic current properties, suggesting that these voltage sensors are involved in CaV1.2 activation. This view is supported by an obligatory model, in which activation of VSDs II and III is necessary to open the pore. When these data were interpreted in view of an allosteric model, where pore opening is intrinsically independent but biased by VSD activation, VSDs II and III were each found to supply ∼50 meV (∼2 kT), amounting to ∼85% of the total energy, toward stabilizing the open state, with a smaller contribution from VSD I (∼16 meV). VSD IV did not appear to participate in channel opening.
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