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Article: Role of SK Ca and IK Ca in endothelium-dependent hyperpolarizations of the guinea-pig isolated carotid artery

TitleRole of SK Ca and IK Ca in endothelium-dependent hyperpolarizations of the guinea-pig isolated carotid artery
Authors
Keywords14,15-EEZE
Ca 2+-activated potassium channel
Cytochrome P450, smooth muscle
EDHF
Endothelium
TRAM-34
UCL 1684
Issue Date2005
PublisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0007-1188&site=1
Citation
British Journal Of Pharmacology, 2005, v. 144 n. 4, p. 477-485 How to Cite?
AbstractThis study was designed to determine whether the endothelium-dependent hyperpolarizations evoked by acetylcholine in guinea-pig carotid artery involve a cytochrome P450 metabolite and whether they are linked to the activation of two distinct populations of endothelial K Ca channels, SK Ca and IK Ca. The membrane potential was recorded in the vascular smooth muscle cells of the guinea-pig isolated carotid artery. All the experiments were performed in the presence of N ω-L-nitro arginine (100 μM) and indomethacin (5 μM). Under control conditions (Ca 2+: 2.5 mM), acetylcholine (10 nM to 10 μM) induced a concentration- and endothelium-dependent hyperpolarization of the vascular smooth muscle cells. Two structurally different specific blockers of SK Ca, apamin (0.5 μM) or UCL 1684 (10 μM). produced a partial but significant inhibition of the hyperpolarization evoked by acetylcholine whereas charybdotoxin (0.1 μM) and TRAM-34 (10 μM), a nonpeptidic and specific blocker of IK Ca. were ineffective. In contrast, the combinations of apamin plus charybdotoxin, apamin plus TRAM-34 (10 μ) or UCL 1684 (10 μM) plus TRAM-34 (10 μM) virtually abolished the acetylcholine-induced hyperpolarization. In the presence of a combination of apamin and a subeffective dose of TRAM-34 (5 μM), the residual hyperpolarization produced by acetylcholine was not inhibited further by the addition of either an epoxyeicosatrienoic acid antagonist, 14,15-EEZE (10 μM) or the specific blocker of BK Ca, iberiotoxin (0.1 μM). In presence of 0.5 mM Ca 2+, the hyperpolarization in response to acetylcholine (1 μM) was significantly lower than in 2.5 mM Ca 2+. The EDHF-mediated responses became predominantly sensitive to charybdotoxin or TRAM-34 but resistant to apamin. This investigation shows that the production of a cytochrome P450 metabolite, and the subsequent activation of BK Ca, is unlikely to contribute to the EDHF-mediated responses in the guinea-pig carotid artery. Furthermore, the EDHF-mediated response involves the activation of both endothelial IK Ca and SK Ca channels, the activation of either one being able to produce a true hyperpolarization. © 2005 Nature Publishing Group All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/49283
ISSN
2015 Impact Factor: 5.259
2015 SCImago Journal Rankings: 2.368
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorGluais, Pen_HK
dc.contributor.authorEdwards, Gen_HK
dc.contributor.authorWeston, AHen_HK
dc.contributor.authorFalck, JRen_HK
dc.contributor.authorVanhoutte, PMen_HK
dc.contributor.authorFélétou, Men_HK
dc.date.accessioned2008-06-12T06:38:26Z-
dc.date.available2008-06-12T06:38:26Z-
dc.date.issued2005en_HK
dc.identifier.citationBritish Journal Of Pharmacology, 2005, v. 144 n. 4, p. 477-485en_HK
dc.identifier.issn0007-1188en_HK
dc.identifier.urihttp://hdl.handle.net/10722/49283-
dc.description.abstractThis study was designed to determine whether the endothelium-dependent hyperpolarizations evoked by acetylcholine in guinea-pig carotid artery involve a cytochrome P450 metabolite and whether they are linked to the activation of two distinct populations of endothelial K Ca channels, SK Ca and IK Ca. The membrane potential was recorded in the vascular smooth muscle cells of the guinea-pig isolated carotid artery. All the experiments were performed in the presence of N ω-L-nitro arginine (100 μM) and indomethacin (5 μM). Under control conditions (Ca 2+: 2.5 mM), acetylcholine (10 nM to 10 μM) induced a concentration- and endothelium-dependent hyperpolarization of the vascular smooth muscle cells. Two structurally different specific blockers of SK Ca, apamin (0.5 μM) or UCL 1684 (10 μM). produced a partial but significant inhibition of the hyperpolarization evoked by acetylcholine whereas charybdotoxin (0.1 μM) and TRAM-34 (10 μM), a nonpeptidic and specific blocker of IK Ca. were ineffective. In contrast, the combinations of apamin plus charybdotoxin, apamin plus TRAM-34 (10 μ) or UCL 1684 (10 μM) plus TRAM-34 (10 μM) virtually abolished the acetylcholine-induced hyperpolarization. In the presence of a combination of apamin and a subeffective dose of TRAM-34 (5 μM), the residual hyperpolarization produced by acetylcholine was not inhibited further by the addition of either an epoxyeicosatrienoic acid antagonist, 14,15-EEZE (10 μM) or the specific blocker of BK Ca, iberiotoxin (0.1 μM). In presence of 0.5 mM Ca 2+, the hyperpolarization in response to acetylcholine (1 μM) was significantly lower than in 2.5 mM Ca 2+. The EDHF-mediated responses became predominantly sensitive to charybdotoxin or TRAM-34 but resistant to apamin. This investigation shows that the production of a cytochrome P450 metabolite, and the subsequent activation of BK Ca, is unlikely to contribute to the EDHF-mediated responses in the guinea-pig carotid artery. Furthermore, the EDHF-mediated response involves the activation of both endothelial IK Ca and SK Ca channels, the activation of either one being able to produce a true hyperpolarization. © 2005 Nature Publishing Group All rights reserved.en_HK
dc.format.extent388 bytes-
dc.format.mimetypetext/html-
dc.languageengen_HK
dc.publisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0007-1188&site=1en_HK
dc.relation.ispartofBritish Journal of Pharmacologyen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject14,15-EEZEen_HK
dc.subjectCa 2+-activated potassium channelen_HK
dc.subjectCytochrome P450, smooth muscleen_HK
dc.subjectEDHFen_HK
dc.subjectEndotheliumen_HK
dc.subjectTRAM-34en_HK
dc.subjectUCL 1684en_HK
dc.titleRole of SK Ca and IK Ca in endothelium-dependent hyperpolarizations of the guinea-pig isolated carotid arteryen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0007-1188&volume=144&issue=4&spage=477&epage=485&date=2005&atitle=Role+of+SK(Ca)+and+IK(Ca)+in+endothelium-dependent+hyperpolarizations+of+the+guinea-pig+isolated+carotid+arteryen_HK
dc.identifier.emailVanhoutte, PM: vanhoutt@hku.hken_HK
dc.identifier.authorityVanhoutte, PM=rp00238en_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.doi10.1038/sj.bjp.0706003en_HK
dc.identifier.pmid15655533-
dc.identifier.pmcidPMC1576024en_HK
dc.identifier.scopuseid_2-s2.0-14844289539en_HK
dc.identifier.hkuros97743-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-14844289539&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume144en_HK
dc.identifier.issue4en_HK
dc.identifier.spage477en_HK
dc.identifier.epage485en_HK
dc.identifier.isiWOS:000227330600004-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridGluais, P=6602456462en_HK
dc.identifier.scopusauthoridEdwards, G=7402317535en_HK
dc.identifier.scopusauthoridWeston, AH=7102913361en_HK
dc.identifier.scopusauthoridFalck, JR=7101749267en_HK
dc.identifier.scopusauthoridVanhoutte, PM=7202304247en_HK
dc.identifier.scopusauthoridFélétou, M=7006461826en_HK

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