{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T10:42:35Z","timestamp":1785494555499,"version":"3.56.0"},"reference-count":68,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T00:00:00Z","timestamp":1683849600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Heart, Lung, and Blood Institute","award":["R01-HL147315"],"award-info":[{"award-number":["R01-HL147315"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Calcium\/voltage-activated potassium channels (BK) control smooth muscle (SM) tone and cerebral artery diameter. They include channel-forming \u03b1 and regulatory \u03b21 subunits, the latter being highly expressed in SM. Both subunits participate in steroid-induced modification of BK activity: \u03b21 provides recognition for estradiol and cholanes, resulting in BK potentiation, whereas \u03b1 suffices for BK inhibition by cholesterol or pregnenolone. Aldosterone can modify cerebral artery function independently of its effects outside the brain, yet BK involvement in aldosterone\u2019s cerebrovascular action and identification of channel subunits, possibly involved in steroid action, remains uninvestigated. Using microscale thermophoresis, we demonstrated that each subunit type presents two recognition sites for aldosterone: at 0.3 and \u226510 \u00b5M for \u03b1 and at 0.3\u20131 \u00b5M and \u2265100 \u00b5M for \u03b21. Next, we probed aldosterone on SM BK activity and diameter of middle cerebral artery (MCA) isolated from \u03b21\u2212\/\u2212 vs. wt mice. Data showed that \u03b21 leftward-shifted aldosterone-induced BK activation, rendering EC50~3 \u03bcM and ECMAX \u2265 10 \u03bcM, at which BK activity increased by 20%. At similar concentrations, aldosterone mildly yet significantly dilated MCA independently of circulating and endothelial factors. Lastly, aldosterone-induced MCA dilation was lost in \u03b21\u2212\/\u2212 mice. Therefore, \u03b21 enables BK activation and MCA dilation by low \u00b5M aldosterone.<\/jats:p>","DOI":"10.3390\/ijms24108704","type":"journal-article","created":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T02:56:57Z","timestamp":1684119417000},"page":"8704","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Differential Functional Contribution of BK Channel Subunits to Aldosterone-Induced Channel Activation in Vascular Smooth Muscle and Eventual Cerebral Artery Dilation"],"prefix":"10.3390","volume":"24","author":[{"given":"Steven C.","family":"Mysiewicz","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Addiction Science, and Toxicology, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN 38103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sydney M.","family":"Hawks","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Addiction Science, and Toxicology, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN 38103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0655-2319","authenticated-orcid":false,"given":"Anna N.","family":"Bukiya","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Addiction Science, and Toxicology, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN 38103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4210-0096","authenticated-orcid":false,"given":"Alex M.","family":"Dopico","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Addiction Science, and Toxicology, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN 38103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1046\/j.1523-1755.2000.00979.x","article-title":"Nongenomic effects of steroids on the nicotinic acetylcholine receptor","volume":"57","author":"Barrantes","year":"2000","journal-title":"Kidney Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"31154","DOI":"10.1074\/jbc.M113.496117","article-title":"Identification of Novel Cholesterol-binding Regions in Kir2 Channels","volume":"288","author":"Noskov","year":"2013","journal-title":"J. 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