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- Title
Kaempferol stimulates large conductance Ca2+ -activated K+ (BKCa) channels in human umbilical vein endothelial cells via a cAMP/PKA-dependent pathway.
- Authors
Xu, Y. C.; Leung, G. P. H.; Wong, P. Y. D.; Vanhoutte, P. M.; Man, R. Y. K.
- Abstract
Background 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 EC50 value of 2.5±0.02 μM. This kaempferol-induced current was abolished by large conductance Ca2+-activated K+ (BKCa) channel blockers, such as iberiotoxin (IbTX) and charybdotoxin (ChTX), whereas the small conductance Ca2+-activated K+ (SKCa) channel blocker, apamin, and the voltage-dependent K+ (KV) channel blocker, 4-aminopyridine, had no effect. Cell-attached patches demonstrated that kaempferol increased the open probability of BkCa channels in HUVECs. Clamping intracellular Ca2+ 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 BKCa channels by kaempferol caused membrane hyperpolarization of HUVECs.Conclusion and implications:These results demonstrate that kaempferol activates the opening of BKCa channels in HUVECs via a cAMP/PKA-dependent pathway, resulting in membrane hyperpolarization. This mechanism may partly account for the vasodilator effects of kaempferol.British Journal of Pharmacology (2008) 154, 1247–1253; doi:10.1038/bjp.2008.194; published online 19 May 2008
- Subjects
VASODILATORS; CELLS; ELECTROPHYSIOLOGY; BIOLOGICAL membranes; GUANYLATE cyclase; IN vitro studies; RESEARCH; CYCLIC adenylic acid; UMBILICAL veins; MUSCLE contraction; RESEARCH methodology; MEDICAL cooperation; EVALUATION research; CELLULAR signal transduction; NUCLEOTIDES; COMPARATIVE studies; TRANSFERASES; FLAVONOLS; EPITHELIAL cells; MEMBRANE proteins; CYTOLOGY; ALGORITHMS
- Publication
British Journal of Pharmacology, 2008, Vol 154, Issue 6, p1247
- ISSN
0007-1188
- Publication type
journal article
- DOI
10.1038/bjp.2008.194