File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Nitric oxide deficit in chronic intermittent hypoxia impairs large conductance calcium-activated potassium channel activity in rat hippocampal neurons

TitleNitric oxide deficit in chronic intermittent hypoxia impairs large conductance calcium-activated potassium channel activity in rat hippocampal neurons
Authors
KeywordsHippocampus
Intermittent hypoxia
Nitric oxide
Potassium channel
S-Nitrosylation
Sleep apnea
Issue Date2008
PublisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/freeradbiomed
Citation
Free Radical Biology And Medicine, 2008, v. 44 n. 4, p. 547-557 How to Cite?
AbstractSleep apnea associated with chronic intermittent hypoxia (IH) impairs hippocampal functions but the pathogenic mechanisms involving dysfunction of nitric oxide (NO) and ionic channels remain unclear. We examined the hypothesis that hippocampal NO deficit impairs the activity of large conductance calcium-activated potassium (BK) channels in rats with chronic IH, mimicking conditions in patients with sleep apnea. A patch-clamp study was performed on hippocampal CA1 neurons acutely dissociated from IH and control rats. The levels of endogenous NO and intracellular calcium in the CA1 region of the hippocampal slices were measured respectively by electrochemical microsensors and spectrofluorometry. We found that the open probability of BK channels remarkably decreased in the CA1 pyramidal neurons in a time-dependent manner with the IH treatment, without changes in the unitary conductance and reversal potential. NO donors, SNP or DETA/NO, significantly restored the activity of BK channels in the IH neurons, which was prevented by blockade of S-nitrosylation with NEM or MTSES but not by inhibition of the cGMP pathway with ODQ or 8-bromo-cGMP. Endogenous NO levels were substantially lowered in the IH hippocampus during resting and hypoxia. Also, the level of protein expression of neuronal NO synthase was markedly lessened in the IH neurons with decreased intracellular calcium response to hypoxia. Collectively, the results suggest that the IH-induced NO deficit mediated by a down-regulation of the expression of neuronal NO synthase plays a causative role in the impaired activity of BK channels, which could account for the hippocampal injury in patients with sleep apnea. © 2007 Elsevier Inc. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/81180
ISSN
2015 Impact Factor: 5.784
2015 SCImago Journal Rankings: 2.468
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorTjong, YWen_HK
dc.contributor.authorLi, Men_HK
dc.contributor.authorHung, MWen_HK
dc.contributor.authorWang, Ken_HK
dc.contributor.authorFung, MLen_HK
dc.date.accessioned2010-09-06T08:14:44Z-
dc.date.available2010-09-06T08:14:44Z-
dc.date.issued2008en_HK
dc.identifier.citationFree Radical Biology And Medicine, 2008, v. 44 n. 4, p. 547-557en_HK
dc.identifier.issn0891-5849en_HK
dc.identifier.urihttp://hdl.handle.net/10722/81180-
dc.description.abstractSleep apnea associated with chronic intermittent hypoxia (IH) impairs hippocampal functions but the pathogenic mechanisms involving dysfunction of nitric oxide (NO) and ionic channels remain unclear. We examined the hypothesis that hippocampal NO deficit impairs the activity of large conductance calcium-activated potassium (BK) channels in rats with chronic IH, mimicking conditions in patients with sleep apnea. A patch-clamp study was performed on hippocampal CA1 neurons acutely dissociated from IH and control rats. The levels of endogenous NO and intracellular calcium in the CA1 region of the hippocampal slices were measured respectively by electrochemical microsensors and spectrofluorometry. We found that the open probability of BK channels remarkably decreased in the CA1 pyramidal neurons in a time-dependent manner with the IH treatment, without changes in the unitary conductance and reversal potential. NO donors, SNP or DETA/NO, significantly restored the activity of BK channels in the IH neurons, which was prevented by blockade of S-nitrosylation with NEM or MTSES but not by inhibition of the cGMP pathway with ODQ or 8-bromo-cGMP. Endogenous NO levels were substantially lowered in the IH hippocampus during resting and hypoxia. Also, the level of protein expression of neuronal NO synthase was markedly lessened in the IH neurons with decreased intracellular calcium response to hypoxia. Collectively, the results suggest that the IH-induced NO deficit mediated by a down-regulation of the expression of neuronal NO synthase plays a causative role in the impaired activity of BK channels, which could account for the hippocampal injury in patients with sleep apnea. © 2007 Elsevier Inc. All rights reserved.en_HK
dc.languageengen_HK
dc.publisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/freeradbiomeden_HK
dc.relation.ispartofFree Radical Biology and Medicineen_HK
dc.rightsFree Radical Biology & Medicine. Copyright © Elsevier Inc.en_HK
dc.subjectHippocampusen_HK
dc.subjectIntermittent hypoxiaen_HK
dc.subjectNitric oxideen_HK
dc.subjectPotassium channelen_HK
dc.subjectS-Nitrosylationen_HK
dc.subjectSleep apneaen_HK
dc.titleNitric oxide deficit in chronic intermittent hypoxia impairs large conductance calcium-activated potassium channel activity in rat hippocampal neuronsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0891-5849&volume=44&issue=4&spage=547&epage=557&date=2008&atitle=Nitric+oxide+deficit+in+chronic+intermittent+hypoxia+impairs+large+conductance+calcium-activated+potassium+channel+activity+in+rat+hippocampal+neuronsen_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/j.freeradbiomed.2007.10.033en_HK
dc.identifier.pmid17996205-
dc.identifier.scopuseid_2-s2.0-38749113411en_HK
dc.identifier.hkuros141458en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-38749113411&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume44en_HK
dc.identifier.issue4en_HK
dc.identifier.spage547en_HK
dc.identifier.epage557en_HK
dc.identifier.eissn1873-4596-
dc.identifier.isiWOS:000253090200007-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridTjong, YW=6507176524en_HK
dc.identifier.scopusauthoridLi, M=15132223400en_HK
dc.identifier.scopusauthoridHung, MW=16744402300en_HK
dc.identifier.scopusauthoridWang, K=7501396814en_HK
dc.identifier.scopusauthoridFung, ML=7101955092en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats