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Article: A conserved ring of charge in mammalian Na + channels: A molecular regulator of the outer pore conformation during slow inactivation

TitleA conserved ring of charge in mammalian Na + channels: A molecular regulator of the outer pore conformation during slow inactivation
Authors
Issue Date2006
PublisherWiley-Blackwell Publishing Ltd.. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0022-3751
Citation
Journal Of Physiology, 2006, v. 576 n. 3, p. 739-754 How to Cite?
AbstractThe molecular mechanisms underlying slow inactivation in sodium channels are elusive. Our results suggest that EEDD, a highly conserved ring of charge in the external vestibule of mammalian voltage-gated sodium channels, undermines slow inactivation. By employing site-directed mutagenesis, we found that charge alterations in this asymmetric yet strong local electrostatic field of the EEDD ring significantly altered the kinetics of slow inactivation gating. Using a non-linear Poisson-Boltzmann equation, quantitative computations of the electrostatic field in a sodium channel structural model suggested a significant electrostatic repulsion between residues E403 and E758 at close proximity. Interestingly, when this electrostatic interaction was eliminated by the double mutation E403C + E758C, the kinetics of recovery from slow inactivation of the double-mutant channel was retarded by 2500% compared to control. These data suggest that the EEDD ring, located within the asymmetric electric field, is a molecular motif that critically modulates slow inactivation in sodium channels. © 2006 The Authors. Journal compilation © 2006 The Physiological Society.
Persistent Identifierhttp://hdl.handle.net/10722/124981
ISSN
2015 Impact Factor: 4.731
2015 SCImago Journal Rankings: 2.670
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorXiong, Wen_HK
dc.contributor.authorFarukhi, YZen_HK
dc.contributor.authorTian, Yen_HK
dc.contributor.authorDisilvestre, Den_HK
dc.contributor.authorLi, RAen_HK
dc.contributor.authorTomaselli, GFen_HK
dc.date.accessioned2010-10-31T11:04:52Z-
dc.date.available2010-10-31T11:04:52Z-
dc.date.issued2006en_HK
dc.identifier.citationJournal Of Physiology, 2006, v. 576 n. 3, p. 739-754en_HK
dc.identifier.issn0022-3751en_HK
dc.identifier.urihttp://hdl.handle.net/10722/124981-
dc.description.abstractThe molecular mechanisms underlying slow inactivation in sodium channels are elusive. Our results suggest that EEDD, a highly conserved ring of charge in the external vestibule of mammalian voltage-gated sodium channels, undermines slow inactivation. By employing site-directed mutagenesis, we found that charge alterations in this asymmetric yet strong local electrostatic field of the EEDD ring significantly altered the kinetics of slow inactivation gating. Using a non-linear Poisson-Boltzmann equation, quantitative computations of the electrostatic field in a sodium channel structural model suggested a significant electrostatic repulsion between residues E403 and E758 at close proximity. Interestingly, when this electrostatic interaction was eliminated by the double mutation E403C + E758C, the kinetics of recovery from slow inactivation of the double-mutant channel was retarded by 2500% compared to control. These data suggest that the EEDD ring, located within the asymmetric electric field, is a molecular motif that critically modulates slow inactivation in sodium channels. © 2006 The Authors. Journal compilation © 2006 The Physiological Society.en_HK
dc.languageengen_HK
dc.publisherWiley-Blackwell Publishing Ltd.. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0022-3751en_HK
dc.relation.ispartofJournal of Physiologyen_HK
dc.subject.meshAmino Acid Motifs - physiology-
dc.subject.meshIon Channel Gating - physiology-
dc.subject.meshMembrane Potentials - physiology-
dc.subject.meshPorins - chemistry - genetics - physiology-
dc.subject.meshSodium Channels - chemistry - genetics - physiology-
dc.titleA conserved ring of charge in mammalian Na + channels: A molecular regulator of the outer pore conformation during slow inactivationen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0022-3751&volume=576&issue=3&spage=739&epage=754&date=2006&atitle=A+conserved+ring+of+charge+in+mammalian+Na++channels:+a+molecular+regulator+of+the+outer+pore+conformation+during+slow+inactivation-
dc.identifier.emailLi, RA:ronaldli@hkucc.hku.hken_HK
dc.identifier.authorityLi, RA=rp01352en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1113/jphysiol.2006.115105en_HK
dc.identifier.pmid16873407-
dc.identifier.pmcidPMC1890405-
dc.identifier.scopuseid_2-s2.0-33750402366en_HK
dc.identifier.hkuros183059en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33750402366&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume576en_HK
dc.identifier.issue3en_HK
dc.identifier.spage739en_HK
dc.identifier.epage754en_HK
dc.identifier.isiWOS:000242237200014-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridXiong, W=8670689200en_HK
dc.identifier.scopusauthoridFarukhi, YZ=15046544500en_HK
dc.identifier.scopusauthoridTian, Y=10340915900en_HK
dc.identifier.scopusauthoridDisilvestre, D=6602921075en_HK
dc.identifier.scopusauthoridLi, RA=7404724466en_HK
dc.identifier.scopusauthoridTomaselli, GF=7005223451en_HK
dc.identifier.citeulike914972-

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