ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2003
The position of the fourth segment of domain 4 determines status of the inactivation gate in Na+ channels.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
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- Article
- Changes in Resurgent Sodium Current Contribute to the Hyperexcitability of Muscles in Patients with Paramyotonia Congenita.Biomedicines · 2021Article
- Anomalous enhancement of resurgent NaScientific reports · 2019Article
- The Biophysical Basis Underlying Gating Changes in the p.V1316A Mutant Nav1.7 Channel and the Molecular Pathogenesis of Inherited Erythromelalgia.PLoS biology · 2016Article
- Gating-pore currents demonstrate selective and specific modulation of individual sodium channel voltage-sensors by biological toxins.Molecular pharmacology · 2014Article
- Sequence variations at I260 and A1731 contribute to persistent currents in Drosophila sodium channels.Neuroscience · 2014Article
- Direct evidence that scorpion α-toxins (site-3) modulate sodium channel inactivation by hindrance of voltage-sensor movements.PloS one · 2013Article
- Domain III regulates N-type (CaV2.2) calcium channel closing kinetics.Journal of neurophysiology · 2012Article
- Functional extension of amino acid triads from the fourth transmembrane segment (S4) into its external linker in Shaker K(+) channels.The Journal of biological chemistry · 2011Article
- Elucidation of the molecular basis of selective recognition uncovers the interaction site for the core domain of scorpion alpha-toxins on sodium channels.The Journal of biological chemistry · 2011Article
- Studies of alpha-helicity and intersegmental interactions in voltage-gated Na+ channels: S2D4.PloS one · 2009Article
- The external pore loop interacts with S6 and S3-S4 linker in domain 4 to assume an essential role in gating control and anticonvulsant action in the Na(+) channel.The Journal of general physiology · 2009Article
- Molecular requirements for recognition of brain voltage-gated sodium channels by scorpion alpha-toxins.The Journal of biological chemistry · 2009Article
- The effect of recombinant neurotoxins from the sea anemone Anthopleura sp. on sodium currents of rat cerebral cortical neurons.Cellular and molecular neurobiology · 2008Article
- A hydrophobic element secures S4 voltage sensor in position in resting Shaker K+ channels.The Journal of physiology · 2007Article
- Central charged residues in DIIIS4 regulate deactivation gating in skeletal muscle sodium channels.Cellular and molecular neurobiology · 2007Article
- An inactivation stabilizer of the Na+ channel acts as an opportunistic pore blocker modulated by external Na+.The Journal of general physiology · 2005Article
- Block of tetrodotoxin-resistant Na+ channel pore by multivalent cations: gating modification and Na+ flow dependence.The Journal of general physiology · 2004Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The fourth segment of domain 4 (S4/D4) in Na+ channels is a voltage sensor especially implicated in channel inactivation. Although there has been evidence that S4/D4 moves externally during membrane depolarization, whether (and if so, how) the movement leads to conformational changes of the inactivation gate remains unknown. We added a positive charge just external to the outermost charged residue in S4/D4 by point mutations of residue F1625 (i.e., F1625R and F1625K). The inactivation curves as well as the kinetics of recovery from inactivation in these mutant channels are split into two components, one happening with and the other without channel activation/deactivation. This is as if the "extra" positive charge induces new intermediate positions of S4/D4 and consequently new intermediate inactivation states uncoupled from channel activation/deactivation. The qualitatively similar but quantitatively very different findings between the F1625R and F1625K mutants further suggest a significantly different effect on the inactivation gate by a slight difference in the localization of the positive charge. On the other hand, neutral mutations of residue F1625 do not induce new inactivation states but shift the voltage dependence of different inactivation parameters in the voltage axis, as if only the relative tendency of S4/D4 to stay in its original outermost and innermost positions is altered. We conclude that S4/D4 movement not only decisively but also delicately controls the inactivation gate. Electrostatic interaction between the top charges of S4/D4 and the corresponding countercharges may play an essential role in the determination of S4/D4 position and therefore the inactivation status of the Na+ channel.
Indexed as
Identifiers
12832514PMC6741210W2146929971What OpenQuestion holds
Registered trials
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