{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T14:33:04Z","timestamp":1792679584976,"version":"4.5.0"},"reference-count":60,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2014,8,15]]},"abstract":"\n Background<\/jats:title>\n \n Transient receptor potential C3 (\n TRPC<\/jats:styled-content>\n 3) has been demonstrated to be involved in the regulation of vascular tone through endothelial cell (\n EC<\/jats:styled-content>\n ) hyperpolarization and endothelium\u2010dependent hyperpolarization\u2013mediated vasodilation. However, the mechanism by which\n TRPC<\/jats:styled-content>\n 3 regulates these processes remains unresolved. We tested the hypothesis that endothelial receptor stimulation triggers rapid\n TRPC<\/jats:styled-content>\n 3 trafficking to the plasma membrane, where it provides the source of Ca\n 2+<\/jats:sup>\n influx for small conductance calcium\u2010activated K\n +<\/jats:sup>\n (SK\n Ca<\/jats:sub>\n ) channel activation and sustained\n EC<\/jats:styled-content>\n hyperpolarization.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n Pressurized artery studies were performed with isolated mouse posterior cerebral artery. Treatment with a selective\n TRPC<\/jats:styled-content>\n 3 blocker (Pyr3) produced significant attenuation of endothelium\u2010dependent hyperpolarization\u2013mediated vasodilation and endothelial Ca\n 2+<\/jats:sup>\n response (\n EC<\/jats:styled-content>\n \u2010specific Ca\n 2+<\/jats:sup>\n biosensor) to intraluminal\n ATP<\/jats:styled-content>\n . Pyr3 treatment also resulted in a reduced\n ATP<\/jats:styled-content>\n \u2010stimulated global Ca\n 2+<\/jats:sup>\n and Ca\n 2+<\/jats:sup>\n influx in primary cultures of cerebral endothelial cells. Patch\u2010clamp studies with freshly isolated cerebral\n EC<\/jats:styled-content>\n s demonstrated 2 components of\n EC<\/jats:styled-content>\n hyperpolarization and K\n +<\/jats:sup>\n current activation in response to\n ATP<\/jats:styled-content>\n . The early phase was dependent on intermediate conductance calcium\u2010activated K\n +<\/jats:sup>\n channel activation, whereas the later sustained phase relied on\n \n SK\n C<\/jats:sub>\n <\/jats:styled-content>\n a<\/jats:sub>\n channel activation. The\n \n SK\n C<\/jats:sub>\n <\/jats:styled-content>\n a<\/jats:sub>\n channel\u2013dependent phase was completely blocked with\n TRPC<\/jats:styled-content>\n 3 channel inhibition or in\n ECs<\/jats:styled-content>\n of\n TRPC<\/jats:styled-content>\n 3 knockout mice and correlated with increased trafficking of\n TRPC<\/jats:styled-content>\n 3 (but not\n \n SK\n C<\/jats:sub>\n <\/jats:styled-content>\n a<\/jats:sub>\n channel) to the plasma membrane.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n We propose that\n TRPC<\/jats:styled-content>\n 3 dynamically regulates\n \n SK\n C<\/jats:sub>\n <\/jats:styled-content>\n a<\/jats:sub>\n channel activation through receptor\u2010dependent trafficking to the plasma membrane, where it provides the source of Ca\n 2+<\/jats:sup>\n influx for sustained\n \n SK\n C<\/jats:sub>\n <\/jats:styled-content>\n a<\/jats:sub>\n channel activation,\n EC<\/jats:styled-content>\n hyperpolarization, and endothelium\u2010dependent hyperpolarization\u2013mediated vasodilation.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.114.000913","type":"journal-article","created":{"date-parts":[[2014,8,21]],"date-time":"2014-08-21T03:40:03Z","timestamp":1408592403000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":52,"title":["Activation of Endothelial Transient Receptor Potential C3 Channel Is Required for Small Conductance Calcium\u2010Activated Potassium Channel Activation and Sustained Endothelial Hyperpolarization and Vasodilation of Cerebral Artery"],"prefix":"10.1161","volume":"3","author":[{"given":"Mikhail Y.","family":"Kochukov","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Baylor College of Medicine, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adithya","family":"Balasubramanian","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Baylor College of Medicine, Houston, 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