ArticleProceedings of the National Academy of Sciences of the United States of America2012
Crystallographic basis for calcium regulation of sodium channels.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
87 citing papers in PubMed, 1 synthesis or guideline pooled it, 134 citations in OpenAlex.
- Calmodulation meta-analysis: predicting calmodulin binding via canonical motif clustering.The Journal of general physiology · 2014Pooled it
- Calmodulin acts as a selective switch in FGF12A-mediated regulation of the cardiac sodium channel Nav1.5.The Journal of biological chemistry · 2026Article
- Calcium interaction with Nav1.5 via FGF12A and CaM binding.bioRxiv : the preprint server for biology · 2026Article
- A robust expression system reveals distinct gating mechanisms and calmodulin regulation of NaScience advances · 2025Article
- An integrative approach to protein sequence design through multiobjective optimization.PLoS computational biology · 2024Article
- Hyperexcitability of muscle spindle afferents in jaw-closing muscles in experimental myalgia: Evidence for large primary afferents involvement in chronic pain.Experimental physiology · 2024Review
- High calcium concentrations reduce cellular excitability of mouse MNTB neurons.Brain research · 2023Article
- Feedback contributions to excitation-contraction coupling in native functioning striated muscle.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Lanthanides as Calcium Mimetic Species in Calcium-Signaling/Buffering Proteins: The Effect of Lanthanide Type on the CaInternational journal of molecular sciences · 2023Article
- Machine learning in computational modelling of membrane protein sequences and structures: From methodologies to applications.Computational and structural biotechnology journal · 2023Review
- BIOLOGICAL ANTIARRHYTHMICS-SODIUM CHANNEL INTERACTING PROTEINS.Transactions of the American Clinical and Climatological Association · 2023Article
- Calmodulin mutations affecting Gly114 impair binding to the NaFrontiers in pharmacology · 2023Article
- Mechanisms and physiological implications of cooperative gating of clustered ion channels.Physiological reviews · 2022Review
- Late Sodium Current of the Heart: Where Do We Stand and Where Are We Going?Pharmaceuticals (Basel, Switzerland) · 2022Review
- NaStructure (London, England : 1993) · 2021Article
- Late sodium current and calcium homeostasis in arrhythmogenesis.Channels (Austin, Tex.) · 2021Review
- Late NaPharmaceuticals (Basel, Switzerland) · 2021Article
- Ca2+-dependent modulation of voltage-gated myocyte sodium channels.Biochemical Society transactions · 2021Review
- Ventricular voltage-gated ion channels: Detection, characteristics, mechanisms, and drug safety evaluation.Clinical and translational medicine · 2021Review
- Calmodulin Interactions with Voltage-Gated Sodium Channels.International journal of molecular sciences · 2021Review
27 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Voltage-gated sodium channels underlie the rapid regenerative upstroke of action potentials and are modulated by cytoplasmic calcium ions through a poorly understood mechanism. We describe the 1.35 Å crystal structure of Ca(2+)-bound calmodulin (Ca(2+)/CaM) in complex with the inactivation gate (DIII-IV linker) of the cardiac sodium channel (Na(V)1.5). The complex harbors the positions of five disease mutations involved with long Q-T type 3 and Brugada syndromes. In conjunction with isothermal titration calorimetry, we identify unique inactivation-gate mutations that enhance or diminish Ca(2+)/CaM binding, which, in turn, sensitize or abolish Ca(2+) regulation of full-length channels in electrophysiological experiments. Additional biochemical experiments support a model whereby a single Ca(2+)/CaM bridges the C-terminal IQ motif to the DIII-IV linker via individual N and C lobes, respectively. The data suggest that Ca(2+)/CaM destabilizes binding of the inactivation gate to its receptor, thus biasing inactivation toward more depolarized potentials.
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Registered trials
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.