{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T02:31:04Z","timestamp":1790735464677,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2011,3,4]],"date-time":"2011-03-04T00:00:00Z","timestamp":1299196800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2011,4]]},"abstract":"<jats:p><jats:bold>BACKGROUND AND PURPOSE<\/jats:bold> Transient receptor potential canonical 5 (TRPC5) channels are widely expressed, including in the CNS, where they potentiate fear responses. They also contribute to other non\u2010selective cation channels that are stimulated by G\u2010protein\u2010coupled receptor agonists and lipid and redox factors. Steroids are known to modulate fear and anxiety states, and we therefore investigated whether TRPC5 exhibited sensitivity to steroids.<\/jats:p><jats:p><jats:bold>EXPERIMENTAL APPROACH<\/jats:bold> Human TRPC5 channels were conditionally expressed in HEK293 cells and studied using intracellular Ca<jats:sup>2+<\/jats:sup> measurement, whole\u2010cell voltage\u2010clamp and excised patch techniques. For comparison, control experiments were performed with cells lacking TRPC5 channels or expressing another TRP channel, TRPM2. Native TRPC channel activity was recorded from vascular smooth muscle cells.<\/jats:p><jats:p><jats:bold>KEY RESULTS<\/jats:bold> Extracellular application of pregnenolone sulphate, pregnanolone sulphate, pregnanolone, progesterone or dihydrotestosterone inhibited TRPC5 activity within 1\u20132\u2003min. Dehydroepiandrosterone sulphate or 17\u03b2\u2010oestradiol had weak inhibitory effects. Pregnenolone, and allopregnanolone, a progesterone metabolite and stereo\u2010isomer of pregnanolone, all had no effects. Progesterone was the most potent of the steroids, especially against TRPC5 channel activity evoked by sphingosine\u20101\u2010phosphate. In outside\u2010out patch recordings, bath\u2010applied progesterone and dihydrotestosterone had strong and reversible effects, suggesting relatively direct mechanisms of action. Progesterone inhibited native TRPC5\u2010containing channel activity, evoked by oxidized phospholipid.<\/jats:p><jats:p><jats:bold>CONCLUSIONS AND IMPLICATIONS<\/jats:bold> Our data suggest that TRPC5 channels are susceptible to relatively direct and rapid stereo\u2010selective steroid modulation, leading to channel inhibition. The study adds to growing appreciation of TRP channels as non\u2010genomic steroid sensors.<\/jats:p>","DOI":"10.1111\/j.1476-5381.2010.01136.x","type":"journal-article","created":{"date-parts":[[2010,11,25]],"date-time":"2010-11-25T13:10:29Z","timestamp":1290690629000},"page":"1509-1520","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Stereo\u2010selective inhibition of transient receptor potential TRPC5 cation channels by neuroactive 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