ArticleThe Journal of general physiology2014
Asymmetric functional contributions of acidic and aromatic side chains in sodium channel voltage-sensor domains.
Article in The Journal of general physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 44 citations in OpenAlex.
- Voltage-sensing domains: structural and functional diversity.European biophysics journal : EBJ · 2026Review
- SCN3B is an Anti-breast Cancer Molecule with Migration Inhibition Effect.Biochemical genetics · 2026Article
- The differential impacts of equivalent gating-charge mutations in voltage-gated sodium channels.The Journal of general physiology · 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
- ELUCIDATING THE DIFFERENTIAL IMPACTS OF EQUIVALENT GATING-CHARGE MUTATIONS IN VOLTAGE-GATED SODIUM CHANNELS.bioRxiv : the preprint server for biology · 2024Article
- Article
- The road to evolution of ProTx2: how to be a subtype-specific inhibition of human NaFrontiers in pharmacology · 2024Article
- Fifty years of gating currents and channel gating.The Journal of general physiology · 2023Review
- Mechanistic insights into robust cardiac IeLife · 2023Article
- Mechanistic insights into robust cardiac IbioRxiv : the preprint server for biology · 2023Article
- Roles for Countercharge in the Voltage Sensor Domain of Ion Channels.Frontiers in pharmacology · 2020Review
- Using voltage-sensor toxins and their molecular targets to investigate NaThe Journal of physiology · 2018Review
- Orthogonality of Pyrrolysine tRNA in the Xenopus oocyte.Scientific reports · 2018Article
- Substitutions of the S4DIV R2 residue (R1451) in NaScientific reports · 2018Article
- Sequence determinants of subtype-specific actions of KCNQ channel openers.The Journal of physiology · 2017Article
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- Article
- Arginine side chain interactions and the role of arginine as a gating charge carrier in voltage sensitive ion channels.Scientific reports · 2016Article
- Molecular Interactions in the Voltage Sensor Controlling Gating Properties of CaV Calcium Channels.Structure (London, England : 1993) · 2016Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Voltage-gated sodium (NaV) channels mediate electrical excitability in animals. Despite strong sequence conservation among the voltage-sensor domains (VSDs) of closely related voltage-gated potassium (KV) and NaV channels, the functional contributions of individual side chains in Nav VSDs remain largely enigmatic. To this end, natural and unnatural side chain substitutions were made in the S2 hydrophobic core (HC), the extracellular negative charge cluster (ENC), and the intracellular negative charge cluster (INC) of the four VSDs of the skeletal muscle sodium channel isoform (NaV1.4). The results show that the highly conserved aromatic side chain constituting the S2 HC makes distinct functional contributions in each of the four NaV domains. No obvious cation-pi interaction exists with nearby S4 charges in any domain, and natural and unnatural mutations at these aromatic sites produce functional phenotypes that are different from those observed previously in Kv VSDs. In contrast, and similar to results obtained with Kv channels, individually neutralizing acidic side chains with synthetic derivatives and with natural amino acid substitutions in the INC had little or no effect on the voltage dependence of activation in any of the four domains. Interestingly, countercharge was found to play an important functional role in the ENC of DI and DII, but not DIII and DIV. These results suggest that electrostatic interactions with S4 gating charges are unlikely in the INC and only relevant in the ENC of DI and DII. Collectively, our data highlight domain-specific functional contributions of highly conserved side chains in NaV VSDs.
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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.