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Article: Kaempferol stimulates large conductance Ca 2+-activated K + (BK Ca) channels in human umbilical vein endothelial cells via a cAMP/PKA-dependent pathway

TitleKaempferol stimulates large conductance Ca 2+-activated K + (BK Ca) channels in human umbilical vein endothelial cells via a cAMP/PKA-dependent pathway
Authors
Issue Date2008
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, 2008, v. 154 n. 6, p. 1247-1253 How to Cite?
AbstractBackground and purpose: Kaempferol has been shown to possess a vasodilator effect but its mechanism of action remains unclear. In this study, experiments were carried out to study the effect of kaempferol on K + channels in endothelial cells. Experimental approach: K + channel activities in human umbilical vein endothelial cells (HUVECs) were studied by conventional whole cell and cell-attached patch-clamp electrophysiology. Key results: Kaempferol stimulated an outward-rectifying current in HUVECs in a dose-dependent manner with an EC 50 value of 2.5±0.02 μM. This kaempferol-induced current was abolished by large conductance Ca 2+-activated K + (BK Ca) channel blockers, such as iberiotoxin (IbTX) and charybdotoxin (ChTX), whereas the small conductance Ca 2+-activated K + (SK Ca) channel blocker, apamin, and the voltage-dependent K + (K V) channel blocker, 4-aminopyridine, had no effect. Cell-attached patches demonstrated that kaempferol increased the open probability of Bk Ca channels in HUVECs. Clamping intracellular Ca 2+ did not prevent kaempferol-induced increases in outward current. In addition, the kaempferol-induced current was diminished by the adenylyl cyclase inhibitor SQ22536, the cAMP antagonist Rp-8-Br-cAMP and the PKA inhibitor KT5720, but was not affected by the guanylyl cyclase inhibitor ODQ, the cGMP antagonist Rp-8-Br-cGMP and the PKG inhibitor KT5823. The activation of BK Ca channels by kaempferol caused membrane hyperpolarization of HUVECs. Conclusion and implications: These results demonstrate that kaempferol activates the opening of BK Ca channels in HUVECs via a cAMP/PKA-dependent pathway, resulting in membrane hyperpolarization. This mechanism may partly account for the vasodilator effects of kaempferol. © 2008 Nature Publishing Group All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/171368
ISSN
2015 Impact Factor: 5.259
2015 SCImago Journal Rankings: 2.368
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorXu, YCen_US
dc.contributor.authorLeung, GPHen_US
dc.contributor.authorWong, PYDen_US
dc.contributor.authorVanhoutte, PMen_US
dc.contributor.authorMan, RYKen_US
dc.date.accessioned2012-10-30T06:13:39Z-
dc.date.available2012-10-30T06:13:39Z-
dc.date.issued2008en_US
dc.identifier.citationBritish Journal Of Pharmacology, 2008, v. 154 n. 6, p. 1247-1253en_US
dc.identifier.issn0007-1188en_US
dc.identifier.urihttp://hdl.handle.net/10722/171368-
dc.description.abstractBackground and purpose: Kaempferol has been shown to possess a vasodilator effect but its mechanism of action remains unclear. In this study, experiments were carried out to study the effect of kaempferol on K + channels in endothelial cells. Experimental approach: K + channel activities in human umbilical vein endothelial cells (HUVECs) were studied by conventional whole cell and cell-attached patch-clamp electrophysiology. Key results: Kaempferol stimulated an outward-rectifying current in HUVECs in a dose-dependent manner with an EC 50 value of 2.5±0.02 μM. This kaempferol-induced current was abolished by large conductance Ca 2+-activated K + (BK Ca) channel blockers, such as iberiotoxin (IbTX) and charybdotoxin (ChTX), whereas the small conductance Ca 2+-activated K + (SK Ca) channel blocker, apamin, and the voltage-dependent K + (K V) channel blocker, 4-aminopyridine, had no effect. Cell-attached patches demonstrated that kaempferol increased the open probability of Bk Ca channels in HUVECs. Clamping intracellular Ca 2+ did not prevent kaempferol-induced increases in outward current. In addition, the kaempferol-induced current was diminished by the adenylyl cyclase inhibitor SQ22536, the cAMP antagonist Rp-8-Br-cAMP and the PKA inhibitor KT5720, but was not affected by the guanylyl cyclase inhibitor ODQ, the cGMP antagonist Rp-8-Br-cGMP and the PKG inhibitor KT5823. The activation of BK Ca channels by kaempferol caused membrane hyperpolarization of HUVECs. Conclusion and implications: These results demonstrate that kaempferol activates the opening of BK Ca channels in HUVECs via a cAMP/PKA-dependent pathway, resulting in membrane hyperpolarization. This mechanism may partly account for the vasodilator effects of kaempferol. © 2008 Nature Publishing Group All rights reserved.en_US
dc.languageengen_US
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_US
dc.relation.ispartofBritish Journal of Pharmacologyen_US
dc.subject.mesh8-Bromo Cyclic Adenosine Monophosphate - Pharmacologyen_US
dc.subject.meshAlgorithmsen_US
dc.subject.meshCyclic Amp - Physiologyen_US
dc.subject.meshCyclic Amp-Dependent Protein Kinases - Physiologyen_US
dc.subject.meshElectrophysiologyen_US
dc.subject.meshEndothelial Cells - Drug Effects - Metabolismen_US
dc.subject.meshFemaleen_US
dc.subject.meshHumansen_US
dc.subject.meshKaempferols - Pharmacologyen_US
dc.subject.meshLarge-Conductance Calcium-Activated Potassium Channels - Agonistsen_US
dc.subject.meshMuscle Relaxation - Drug Effectsen_US
dc.subject.meshPatch-Clamp Techniquesen_US
dc.subject.meshSignal Transduction - Drug Effectsen_US
dc.subject.meshUmbilical Veins - Cytology - Drug Effectsen_US
dc.titleKaempferol stimulates large conductance Ca 2+-activated K + (BK Ca) channels in human umbilical vein endothelial cells via a cAMP/PKA-dependent pathwayen_US
dc.typeArticleen_US
dc.identifier.emailLeung, GPH:gphleung@hkucc.hku.hken_US
dc.identifier.emailVanhoutte, PM:vanhoutt@hku.hken_US
dc.identifier.emailMan, RYK:rykman@hkucc.hku.hken_US
dc.identifier.authorityLeung, GPH=rp00234en_US
dc.identifier.authorityVanhoutte, PM=rp00238en_US
dc.identifier.authorityMan, RYK=rp00236en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1038/bjp.2008.194en_US
dc.identifier.pmid18493242-
dc.identifier.scopuseid_2-s2.0-47249109367en_US
dc.identifier.hkuros151130-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-47249109367&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume154en_US
dc.identifier.issue6en_US
dc.identifier.spage1247en_US
dc.identifier.epage1253en_US
dc.identifier.eissn1476-5381-
dc.identifier.isiWOS:000257613300009-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridXu, YC=35106482400en_US
dc.identifier.scopusauthoridLeung, GPH=35963668200en_US
dc.identifier.scopusauthoridWong, PYD=7403980262en_US
dc.identifier.scopusauthoridVanhoutte, PM=7202304247en_US
dc.identifier.scopusauthoridMan, RYK=7004986435en_US

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