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Article: Effects of ion channels on proliferation in cultured human cardiac fibroblasts

TitleEffects of ion channels on proliferation in cultured human cardiac fibroblasts
Authors
Issue Date2011
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/yjmcc
Citation
Journal Of Molecular And Cellular Cardiology, 2011, v. 51 n. 2, p. 198-206 How to Cite?
AbstractOur previous study demonstrated that multiple ion channels were heterogeneously expressed in human cardiac fibroblasts, including a large-conductance Ca 2+-activated K + current (BKCa), a volume-sensitive chloride current (I Cl.vol), and voltage-gated sodium currents (I Na). The present study was designed to examine the possible involvement of these ion channels in proliferation of cultured human cardiac fibroblasts using approaches of cell proliferation assay, whole-cell patch voltage-clamp, siRNA and Western blot analysis. It was found that the blockade of BKCa with paxilline (1-3μM) or I Cl.vol with 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid disodium (DIDS, 100-200μM), but not I Na with tetrodotoxin (0.1-10μM), remarkably suppressed proliferation in human cardiac fibroblasts. Knockdown of KCa1.1 or Clcn3 with specific siRNAs significantly reduced BKCa or I Cl.vol current, mRNA and channel protein levels, and inhibited growth of human cardiac fibroblasts. Flow cytometry analysis showed accumulation of cardiac fibroblasts at G0/G1 phase and reduced cell number in S phase after inhibition of BKCa or I Cl.vol with channel blockers or knock down of the corresponding channels with specific siRNAs; these effects were accompanied by a decreased expression of cyclin D1 and cyclin E. The present results demonstrate the novel information that BKCa and I Cl.vol channels, but not I Na channels, are involved in the regulation of proliferation in cultured human cardiac fibroblasts by promoting cell cycle progression via modulating cyclin D1 and cyclin E expression. © 2011 Elsevier Ltd.
Persistent Identifierhttp://hdl.handle.net/10722/135204
ISSN
2015 Impact Factor: 4.874
2015 SCImago Journal Rankings: 2.522
ISI Accession Number ID
Funding AgencyGrant Number
Research Grant Council of Hong KongHKU 7603/06 M
University of Hong Kong
Funding Information:

This study was supported by a General Research Fund (HKU 7603/06 M) from Research Grant Council of Hong Kong. Dr. Mu-Lan He was supported by a Postdoctoral Fellowship of the University of Hong Kong.

References

 

DC FieldValueLanguage
dc.contributor.authorHe, MLen_HK
dc.contributor.authorLiu, WJen_HK
dc.contributor.authorSun, HYen_HK
dc.contributor.authorWu, Wen_HK
dc.contributor.authorLiu, Jen_HK
dc.contributor.authorTse, HFen_HK
dc.contributor.authorLau, CPen_HK
dc.contributor.authorLi, GRen_HK
dc.date.accessioned2011-07-27T01:29:58Z-
dc.date.available2011-07-27T01:29:58Z-
dc.date.issued2011en_HK
dc.identifier.citationJournal Of Molecular And Cellular Cardiology, 2011, v. 51 n. 2, p. 198-206en_HK
dc.identifier.issn0022-2828en_HK
dc.identifier.urihttp://hdl.handle.net/10722/135204-
dc.description.abstractOur previous study demonstrated that multiple ion channels were heterogeneously expressed in human cardiac fibroblasts, including a large-conductance Ca 2+-activated K + current (BKCa), a volume-sensitive chloride current (I Cl.vol), and voltage-gated sodium currents (I Na). The present study was designed to examine the possible involvement of these ion channels in proliferation of cultured human cardiac fibroblasts using approaches of cell proliferation assay, whole-cell patch voltage-clamp, siRNA and Western blot analysis. It was found that the blockade of BKCa with paxilline (1-3μM) or I Cl.vol with 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid disodium (DIDS, 100-200μM), but not I Na with tetrodotoxin (0.1-10μM), remarkably suppressed proliferation in human cardiac fibroblasts. Knockdown of KCa1.1 or Clcn3 with specific siRNAs significantly reduced BKCa or I Cl.vol current, mRNA and channel protein levels, and inhibited growth of human cardiac fibroblasts. Flow cytometry analysis showed accumulation of cardiac fibroblasts at G0/G1 phase and reduced cell number in S phase after inhibition of BKCa or I Cl.vol with channel blockers or knock down of the corresponding channels with specific siRNAs; these effects were accompanied by a decreased expression of cyclin D1 and cyclin E. The present results demonstrate the novel information that BKCa and I Cl.vol channels, but not I Na channels, are involved in the regulation of proliferation in cultured human cardiac fibroblasts by promoting cell cycle progression via modulating cyclin D1 and cyclin E expression. © 2011 Elsevier Ltd.en_HK
dc.languageengen_US
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/yjmccen_HK
dc.relation.ispartofJournal of Molecular and Cellular Cardiologyen_HK
dc.rightsNOTICE: this is the author’s version of a work that was accepted for publication in <Journal title>. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in PUBLICATION, [VOL#, ISSUE#, (DATE)] DOI#en_US
dc.subject.meshCell Cycle - drug effects - geneticsen_HK
dc.subject.meshCell Proliferation - drug effectsen_HK
dc.subject.meshCells, Cultureden_HK
dc.subject.meshCyclin D1 - genetics - metabolismen_HK
dc.subject.meshCyclin E - genetics - metabolismen_HK
dc.subject.meshFibroblasts - cytology - metabolismen_HK
dc.subject.meshGene Expression Regulation - drug effectsen_HK
dc.subject.meshHumansen_HK
dc.subject.meshIndoles - pharmacologyen_HK
dc.subject.meshIon Channels - antagonists & inhibitors - genetics - metabolismen_HK
dc.subject.meshMembrane Potentials - drug effects - geneticsen_HK
dc.subject.meshMyocardium - cytology - metabolismen_HK
dc.subject.meshPotassium Channel Blockers - pharmacologyen_HK
dc.subject.meshRNA, Small Interfering - genetics - metabolismen_HK
dc.titleEffects of ion channels on proliferation in cultured human cardiac fibroblastsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0022-2828&volume=51&issue=2&spage=198&epage=206&date=2011&atitle=Effects+of+ion+channels+on+proliferation+in+cultured+human+cardiac+fibroblastsen_US
dc.identifier.emailTse, HF:hftse@hkucc.hku.hken_HK
dc.identifier.emailLi, GR:grli@hkucc.hku.hken_HK
dc.identifier.authorityTse, HF=rp00428en_HK
dc.identifier.authorityLi, GR=rp00476en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.yjmcc.2011.05.008en_HK
dc.identifier.pmid21620856-
dc.identifier.scopuseid_2-s2.0-79959529819en_HK
dc.identifier.hkuros186579en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79959529819&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume51en_HK
dc.identifier.issue2en_HK
dc.identifier.spage198en_HK
dc.identifier.epage206en_HK
dc.identifier.isiWOS:000292578500007-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridHe, ML=7402609178en_HK
dc.identifier.scopusauthoridLiu, WJ=54380301800en_HK
dc.identifier.scopusauthoridSun, HY=54380981600en_HK
dc.identifier.scopusauthoridWu, W=54381013900en_HK
dc.identifier.scopusauthoridLiu, J=36014680100en_HK
dc.identifier.scopusauthoridTse, HF=7006070805en_HK
dc.identifier.scopusauthoridLau, CP=7401968501en_HK
dc.identifier.scopusauthoridLi, GR=7408462932en_HK
dc.identifier.citeulike9374592-

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