ArticleThe Journal of general physiology2016
The α2δ-1 subunit remodels CaV1.2 voltage sensors and allows Ca2+ influx at physiological membrane potentials.
Article in The Journal of general physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35 citing papers in PubMed, 56 citations in OpenAlex.
- Voltage-sensing domains: structural and functional diversity.European biophysics journal : EBJ · 2026Review
- The four voltage-sensing domains of T-type calcium channels activate near the resting membrane potential.Nature communications · 2026Article
- Role of the C-terminal domain in modifying pH-dependent regulation of CaChannels (Austin, Tex.) · 2025Article
- The molecular transition that confers voltage dependence to muscle contraction.Nature communications · 2025Article
- A rich conformational palette underlies human CaNature communications · 2025Article
- α2δ-1-Linked NMDA and AMPA Receptors in Neuropathic Pain and Gabapentinoid Action.Journal of neurochemistry · 2025Review
- Autism-Linked Mutations in αPharmaceuticals (Basel, Switzerland) · 2024Article
- Advances in CaChannels (Austin, Tex.) · 2023Review
- Modulation of CaHandbook of experimental pharmacology · 2023Article
- Pathophysiological Roles of Auxiliary Calcium Channel αHandbook of experimental pharmacology · 2023Article
- Complex effects on CaScientific reports · 2022Article
- The distinct role of the four voltage sensors of the skeletal CaV1.1 channel in voltage-dependent activation.The Journal of general physiology · 2021Article
- Distinct roles for CaV1.1's voltage-sensing domains.The Journal of general physiology · 2021Article
- Voltage sensor movements of CaProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Role of High Voltage-Gated CaCells · 2021Review
- Mechanisms and Regulation of Cardiac CaInternational journal of molecular sciences · 2021Review
- Peripheral Voltage-Gated Cation Channels in Neuropathic Pain and Their Potential as Therapeutic Targets.Frontiers in pain research (Lausanne, Switzerland) · 2021Review
- CaChannels (Austin, Tex.) · 2020Review
- Zn2+-induced changes in Cav2.3 channel function: An electrophysiological and modeling study.The Journal of general physiology · 2020Article
- Different functions of two putative Drosophila αScientific reports · 2020Article
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6 authors at 1 institution in 2 countries.
Funding
Abstract
Excitation-evoked calcium influx across cellular membranes is strictly controlled by voltage-gated calcium channels (CaV), which possess four distinct voltage-sensing domains (VSDs) that direct the opening of a central pore. The energetic interactions between the VSDs and the pore are critical for tuning the channel's voltage dependence. The accessory α2δ-1 subunit is known to facilitate CaV1.2 voltage-dependent activation, but the underlying mechanism is unknown. In this study, using voltage clamp fluorometry, we track the activation of the four individual VSDs in a human L-type CaV1.2 channel consisting of α1C and β3 subunits. We find that, without α2δ-1, the channel complex displays a right-shifted voltage dependence such that currents mainly develop at nonphysiological membrane potentials because of very weak VSD-pore interactions. The presence of α2δ-1 facilitates channel activation by increasing the voltage sensitivity (i.e., the effective charge) of VSDs I-III. Moreover, the α2δ-1 subunit also makes VSDs I-III more efficient at opening the channel by increasing the coupling energy between VSDs II and III and the pore, thus allowing Ca influx within the range of physiological membrane potentials.
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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.