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Article: Increased neuronal excitability after long-term O2 deprivation is mediated mainly by sodium channels

TitleIncreased neuronal excitability after long-term O2 deprivation is mediated mainly by sodium channels
Authors
KeywordsBrain
Electrophysiology
Excitability
Hypoxia
Sodium channel
Tetrodotoxin
Issue Date2000
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/molbrainres
Citation
Molecular Brain Research, 2000, v. 76 n. 2, p. 211-219 How to Cite?
AbstractWe have previously observed that prolonged O2 deprivation alters membrane protein expression and membrane properties in the central nervous system. In this work, we studied the effect of prolonged O2 deprivation on the electrical activity of rat cortical and hippocampal neurons during postnatal development and its relationship to Na+ channels. Rats were raised in low O2 environment (inspired O2 concentration=9.5±0.5%) for 3-4 weeks, starting at an early age (2-3 days old). Using electrophysiologic recordings in brain slices, RNA analysis (northern and slot blots) and saxitoxin (a specific ligand for Na+ channels) binding autoradiography, we addressed two questions: (1) does long-term O2 deprivation alter neuronal excitability in the neocortical and hippocampal neurons during postnatal development? and (2) if so, what are the main mechanisms responsible for the change in excitability in the exposed brain? Our results show that (i) baseline membrane properties of cortical and hippocampal CA1 neurons from rats chronically exposed to hypoxia were not substantially different from those of naive neurons; (ii) acute stress (e.g., hypoxia) elicited a markedly exaggerated response in the exposed neurons as compared to naive ones; (iii) chronic hypoxia tended to increase Na+ channel mRNA and saxitoxin binding density in the cortex and hippocampus as compared to control ones; and (iv) the enhanced neuronal response to acute hypoxia in the exposed cortical and CA1 neurons was considerably attenuated by applying tetrodotoxin, a voltage-sensitive Na+ channel blocker, in a dose-dependent manner. We conclude that prolonged O2 deprivation can lead to major electrophysiological disturbances, especially when exposed neurons are stressed acutely, which renders the chronically exposed neurons more vulnerable to subsequent micro-environmental stress. We suggest that this Na+ channel-related over-excitability is likely to constitute a molecular mechanism for some neurological sequelae, such as epilepsy, resulting from perinatal hypoxic encephalopathy. Copyright (C) 2000 Elsevier Science B.V.
Persistent Identifierhttp://hdl.handle.net/10722/81352
ISSN
2007 Impact Factor: 1.997
2008 SCImago Journal Rankings: 1.457
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorXia, Yen_HK
dc.contributor.authorFung, MLen_HK
dc.contributor.authorO'Reilly, JPen_HK
dc.contributor.authorHaddad, GGen_HK
dc.date.accessioned2010-09-06T08:16:40Z-
dc.date.available2010-09-06T08:16:40Z-
dc.date.issued2000en_HK
dc.identifier.citationMolecular Brain Research, 2000, v. 76 n. 2, p. 211-219en_HK
dc.identifier.issn0169-328Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/81352-
dc.description.abstractWe have previously observed that prolonged O2 deprivation alters membrane protein expression and membrane properties in the central nervous system. In this work, we studied the effect of prolonged O2 deprivation on the electrical activity of rat cortical and hippocampal neurons during postnatal development and its relationship to Na+ channels. Rats were raised in low O2 environment (inspired O2 concentration=9.5±0.5%) for 3-4 weeks, starting at an early age (2-3 days old). Using electrophysiologic recordings in brain slices, RNA analysis (northern and slot blots) and saxitoxin (a specific ligand for Na+ channels) binding autoradiography, we addressed two questions: (1) does long-term O2 deprivation alter neuronal excitability in the neocortical and hippocampal neurons during postnatal development? and (2) if so, what are the main mechanisms responsible for the change in excitability in the exposed brain? Our results show that (i) baseline membrane properties of cortical and hippocampal CA1 neurons from rats chronically exposed to hypoxia were not substantially different from those of naive neurons; (ii) acute stress (e.g., hypoxia) elicited a markedly exaggerated response in the exposed neurons as compared to naive ones; (iii) chronic hypoxia tended to increase Na+ channel mRNA and saxitoxin binding density in the cortex and hippocampus as compared to control ones; and (iv) the enhanced neuronal response to acute hypoxia in the exposed cortical and CA1 neurons was considerably attenuated by applying tetrodotoxin, a voltage-sensitive Na+ channel blocker, in a dose-dependent manner. We conclude that prolonged O2 deprivation can lead to major electrophysiological disturbances, especially when exposed neurons are stressed acutely, which renders the chronically exposed neurons more vulnerable to subsequent micro-environmental stress. We suggest that this Na+ channel-related over-excitability is likely to constitute a molecular mechanism for some neurological sequelae, such as epilepsy, resulting from perinatal hypoxic encephalopathy. Copyright (C) 2000 Elsevier Science B.V.en_HK
dc.languageengen_HK
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/molbrainresen_HK
dc.relation.ispartofMolecular Brain Researchen_HK
dc.rightsMolecular Brain Research. Copyright © Elsevier BV.en_HK
dc.subjectBrainen_HK
dc.subjectElectrophysiologyen_HK
dc.subjectExcitabilityen_HK
dc.subjectHypoxiaen_HK
dc.subjectSodium channelen_HK
dc.subjectTetrodotoxinen_HK
dc.titleIncreased neuronal excitability after long-term O2 deprivation is mediated mainly by sodium channelsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0169-328X&volume=76&spage=211&epage=219&date=2000&atitle=Increased+neuronal+excitability+after+long-term+O2+deprivation+is+mediated+mainly+by+sodium+channelsen_HK
dc.identifier.emailFung, ML: fungml@hkucc.hku.hken_HK
dc.identifier.authorityFung, ML=rp00433en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/S0169-328X(99)00338-1en_HK
dc.identifier.pmid10762696-
dc.identifier.scopuseid_2-s2.0-0034728575en_HK
dc.identifier.hkuros53328en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0034728575&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume76en_HK
dc.identifier.issue2en_HK
dc.identifier.spage211en_HK
dc.identifier.epage219en_HK
dc.identifier.isiWOS:000086584900003-
dc.publisher.placeNetherlandsen_HK
dc.identifier.scopusauthoridXia, Y=7403027616en_HK
dc.identifier.scopusauthoridFung, ML=7101955092en_HK
dc.identifier.scopusauthoridO'Reilly, JP=7202346270en_HK
dc.identifier.scopusauthoridHaddad, GG=7201349499en_HK

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