ArticleBiophysical journal2007
Calcium block of single sodium channels: role of a pore-lining aromatic residue.
Article in Biophysical journal, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 42 citations in OpenAlex.
- Molecular basis for cold and menthol sensing by mammalian TRPM8.Nature communications · 2026Article
- The Cation-π Interaction in Chemistry and Biology.Chemical reviews · 2025Review
- 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
- Tuning phenylalanine fluorination to assess aromatic contributions to protein function and stability in cells.Nature communications · 2023Article
- Mining anion-aromatic interactions in the Protein Data Bank.Chemical science · 2022Article
- Cation-π Interactions and their Functional Roles in Membrane Proteins.Journal of molecular biology · 2021Review
- Lower Ca2+ enhances the K+-induced force depression in normal and HyperKPP mouse muscles.The Journal of general physiology · 2020Article
- Differential Effect on Hippocampal Synaptic Facilitation by the Presynaptic Protein Mover.Frontiers in synaptic neuroscience · 2019Article
- An Underwater Surface-Drying Peptide Inspired by a Mussel Adhesive Protein.Advanced functional materials · 2016Article
- Calcium-Sensing Receptor: A Key Target for Extracellular Calcium Signaling in Neurons.Frontiers in physiology · 2016Review
- Incorporation of Non-Canonical Amino Acids.Advances in experimental medicine and biology · 2015Review
- In vivo incorporation of non-canonical amino acids by using the chemical aminoacylation strategy: a broadly applicable mechanistic tool.Chembiochem : a European journal of chemical biology · 2014Review
- The cation-π interaction.Accounts of chemical research · 2013Article
- A novel mechanism for fine-tuning open-state stability in a voltage-gated potassium channel.Nature communications · 2013Article
- Use-dependent block of the voltage-gated Na(+) channel by tetrodotoxin and saxitoxin: effect of pore mutations that change ionic selectivity.The Journal of general physiology · 2012Article
- Regulation of cardiac Ca(2+) channel by extracellular Na(+).Cell calcium · 2011Article
- Possible roles of exceptionally conserved residues around the selectivity filters of sodium and calcium channels.The Journal of biological chemistry · 2011Article
- An electrostatic interaction between TEA and an introduced pore aromatic drives spring-in-the-door inactivation in Shaker potassium channels.The Journal of general physiology · 2009Article
- The transmembrane tyrosines Y56, Y91 and Y167 play important roles in determining the affinity and transport rate of the rabbit proton-coupled peptide transporter PepT1.The international journal of biochemistry & cell biology · 2009Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Extracellular Ca(2+) ions cause a rapid block of voltage-gated sodium channels, manifest as an apparent reduction of the amplitude of single-channel currents. We examined the influence of residue Tyr-401 in the isoform rNa(V)1.4 on both single-channel conductance and Ca(2+) block. An aromatic residue at this position in the outer mouth of the pore plays a critical role in high-affinity block by the guanidinium toxin tetrodotoxin, primarily due to an electrostatic attraction between the cationic blocker and the system of pi electrons on the aromatic face. We tested whether a similar attraction between small metal cations (Na(+) and Ca(2+)) and this residue would enhance single-channel conductance or pore block, using a series of fluorinated derivatives of phenylalanine at this position. Our results show a monotonic decrease in Ca(2+) block as the aromatic ring is increasingly fluorinated, a result in accord with a cation-pi interaction between Ca(2+) and the aromatic ring. This occurred without a change of single-channel conductance, consistent with a greater electrostatic effect of the pi system on divalent than on monovalent cations. High-level quantum mechanical calculations show that Ca(2+) ions likely do not bind directly to the aromatic ring because of the substantial energetic penalty of dehydrating a Ca(2+) ion. However, the complex of a Ca(2+) ion with its inner hydration shell, Ca(2+)(H(2)O)(6), interacts electrostatically with the aromatic ring in a way that affects the local concentration of Ca(2+) ions in the extracellular vestibule.
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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.