Thanaporn KaewphaleukWattana B. WatanapaUraiwan PanichFaculty of Medicine, Siriraj Hospital, Mahidol University2020-01-272020-01-272019-07-01Life Sciences. Vol.228, (2019), 21-2918790631002432052-s2.0-85064895993https://repository.li.mahidol.ac.th/handle/123456789/50134© 2019 Elsevier Inc. Aims: Ethanol is known to induce NO release and coronary vasorelaxation. Evidence suggests that K + channels, especially a Ca 2+ -activated K + channel (K Ca ), may regulate endothelial NO production. We aimed to investigate the ethanol effect on K + currents in human coronary artery endothelial cells (HCAECs), identify the K + channel type/subtype and signaling pathway involved, and demonstrate the relevance to ethanol-induced NO release. Main methods: Ionic currents of cultured HCAECs were studied using whole-cell patch clamp technique. NO production were measured using the fluorescent probe, 2,3-diaminonaphthalene. Key findings: We found that ethanol significantly potentiated HCAEC current (maximal increase to 155.68 ± 18.93%, 20 mM ethanol, +80 mV; mean ± SEM, n = 9). Ethanol-induced current was significantly inhibited by blockers of IK Ca or SK Ca (intermediate- or small-conductance K Ca ), but not by blocking other K + channels. When other known HCAEC channels were inhibited except IK Ca , 20 mM ethanol significantly increased IK Ca current to 198 ± 25.11% (n = 6), but it could not enhance SK Ca current that was similarly isolated. Moreover, ethanol-induced NO release was prevented by blocking IK Ca channel, adenosine A 2A receptor (A 2A R), G s protein, or protein kinase A (PKA). Significance: This study was the first to demonstrate that acute ethanol exposure could activate endothelial IK Ca channel, via A 2A R-G s -PKA signaling, leading to increased whole-cell current and NO release, which could be an important mechanism underlying ethanol-induced NO release and vasodilation.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyArticleSCOPUS10.1016/j.lfs.2019.04.052