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Article: Structural basis of differences in isoform-specific gating and lidocaine block between cardiac and skeletal muscle sodium channels

TitleStructural basis of differences in isoform-specific gating and lidocaine block between cardiac and skeletal muscle sodium channels
Authors
KeywordsChemicals And Cas Registry Numbers
Issue Date2002
PublisherAmerican Society for Pharmacology and Experimental Therapeutics. The Journal's web site is located at http://www.molpharm.org
Citation
Molecular Pharmacology, 2002, v. 61 n. 1, p. 136-141 How to Cite?
AbstractVoltage-gated Na+ channels underlie rapid conduction in heart and skeletal muscle. Cardiac sodium channels open and close over more negative potentials than do skeletal muscle sodium channels; heart channels are also more sensitive to lidocaine block. The structural basis of these differences is poody understood. We mutated nine isoform-specific υ1 (rat skeletal muscle) channel residues in domain IV to those at equivalent locations in hH1 (human cardiac) channels. Channel constructs were expressed in tsA-201 cells and screened for changes in gating and lidocaine sensitivity. Only L1373E, located in the linker between the S1 and S2 transmembrane segments, shifted activation gating and use-dependent block by lidocaine toward that seen in hH1. The converse mutation, hH1-E1555L, shifted the phenotype of hill to resemble that of υ1. Therefore, we identified a previously unsuspected glutamate-to-leucine isoform-specific variant site (i.e., 1555 in hH1 and 1373 in υ1) that significantly influences gating and drug block in sodium channels. The identification of the residue at this position plays a major role in shaping the responses of sodium channels to voltage and to lidocaine, helping to rationalize the distinctive behavior of cardiac sodium channels.
Persistent Identifierhttp://hdl.handle.net/10722/91487
ISSN
2015 Impact Factor: 3.931
2015 SCImago Journal Rankings: 2.047
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLi, RAen_HK
dc.contributor.authorEnnis, ILen_HK
dc.contributor.authorTomaselli, GFen_HK
dc.contributor.authorMarbán, Een_HK
dc.date.accessioned2010-09-17T10:20:12Z-
dc.date.available2010-09-17T10:20:12Z-
dc.date.issued2002en_HK
dc.identifier.citationMolecular Pharmacology, 2002, v. 61 n. 1, p. 136-141en_HK
dc.identifier.issn0026-895Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/91487-
dc.description.abstractVoltage-gated Na+ channels underlie rapid conduction in heart and skeletal muscle. Cardiac sodium channels open and close over more negative potentials than do skeletal muscle sodium channels; heart channels are also more sensitive to lidocaine block. The structural basis of these differences is poody understood. We mutated nine isoform-specific υ1 (rat skeletal muscle) channel residues in domain IV to those at equivalent locations in hH1 (human cardiac) channels. Channel constructs were expressed in tsA-201 cells and screened for changes in gating and lidocaine sensitivity. Only L1373E, located in the linker between the S1 and S2 transmembrane segments, shifted activation gating and use-dependent block by lidocaine toward that seen in hH1. The converse mutation, hH1-E1555L, shifted the phenotype of hill to resemble that of υ1. Therefore, we identified a previously unsuspected glutamate-to-leucine isoform-specific variant site (i.e., 1555 in hH1 and 1373 in υ1) that significantly influences gating and drug block in sodium channels. The identification of the residue at this position plays a major role in shaping the responses of sodium channels to voltage and to lidocaine, helping to rationalize the distinctive behavior of cardiac sodium channels.en_HK
dc.languageengen_HK
dc.publisherAmerican Society for Pharmacology and Experimental Therapeutics. The Journal's web site is located at http://www.molpharm.orgen_HK
dc.relation.ispartofMolecular Pharmacologyen_HK
dc.subjectChemicals And Cas Registry Numbersen_HK
dc.subject.meshAmino Acids - genetics - metabolismen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshElectrophysiologyen_HK
dc.subject.meshHeart - drug effectsen_HK
dc.subject.meshHumansen_HK
dc.subject.meshLidocaine - chemistry - pharmacologyen_HK
dc.subject.meshMuscle, Skeletal - drug effects - metabolismen_HK
dc.subject.meshMyocardium - metabolismen_HK
dc.subject.meshProtein Isoforms - metabolismen_HK
dc.subject.meshProtein Structure, Tertiaryen_HK
dc.subject.meshRatsen_HK
dc.subject.meshSodium Channel Blockersen_HK
dc.subject.meshSodium Channels - chemistry - physiologyen_HK
dc.titleStructural basis of differences in isoform-specific gating and lidocaine block between cardiac and skeletal muscle sodium channelsen_HK
dc.typeArticleen_HK
dc.identifier.emailLi, RA:ronaldli@hkucc.hku.hken_HK
dc.identifier.authorityLi, RA=rp01352en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1124/mol.61.1.136en_HK
dc.identifier.pmid11752214-
dc.identifier.scopuseid_2-s2.0-0036144123en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0036144123&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume61en_HK
dc.identifier.issue1en_HK
dc.identifier.spage136en_HK
dc.identifier.epage141en_HK
dc.identifier.isiWOS:000173135000016-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLi, RA=7404724466en_HK
dc.identifier.scopusauthoridEnnis, IL=6604033332en_HK
dc.identifier.scopusauthoridTomaselli, GF=7005223451en_HK
dc.identifier.scopusauthoridMarbán, E=8075977300en_HK

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