{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T03:59:15Z","timestamp":1790049555928,"version":"4.0.1"},"reference-count":82,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,28]],"date-time":"2022-12-28T00:00:00Z","timestamp":1672185600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"institutional and departmental funding from the Technical University of Munich"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Dexmedetomidine is a selective \u03b12-adrenoceptor agonist and appears to disinhibit endogenous sleep-promoting pathways, as well as to attenuate noradrenergic excitation. Recent evidence suggests that dexmedetomidine might also directly inhibit hyperpolarization-activated cyclic-nucleotide gated (HCN) channels. We analyzed the effects of dexmedetomidine on native HCN channel function in thalamocortical relay neurons of the ventrobasal complex of the thalamus from mice, performing whole-cell patch-clamp recordings. Over a clinically relevant range of concentrations (1\u201310 \u00b5M), the effects of dexmedetomidine were modest. At a concentration of 10 \u00b5M, dexmedetomidine significantly reduced maximal Ih amplitude (relative reduction: 0.86 [0.78\u20130.91], n = 10, and p = 0.021), yet changes to the half-maximal activation potential V1\/2 occurred exclusively in the presence of the very high concentration of 100 \u00b5M (\u22124,7 [\u22127.5\u2013\u22124.0] mV, n = 10, and p = 0.009). Coincidentally, only the very high concentration of 100 \u00b5M induced a significant deceleration of the fast component of the HCN activation time course (\u03c4fast: +135.1 [+64.7\u2013+151.3] ms, n = 10, and p = 0.002). With the exception of significantly increasing the membrane input resistance (starting at 10 \u00b5M), dexmedetomidine did not affect biophysical membrane properties and HCN channel-mediated parameters of neuronal excitability. Hence, the sedative qualities of dexmedetomidine and its effect on the thalamocortical network are not decisively shaped by direct inhibition of HCN channel function.<\/jats:p>","DOI":"10.3390\/ijms24010519","type":"journal-article","created":{"date-parts":[[2022,12,29]],"date-time":"2022-12-29T02:56:50Z","timestamp":1672282610000},"page":"519","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Sedative Properties of Dexmedetomidine Are Mediated Independently from Native Thalamic Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel Function at Clinically Relevant Concentrations"],"prefix":"10.3390","volume":"24","author":[{"given":"Stefan","family":"Schwerin","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Klinikum Rechts der Isar, Technical University of Munich School of Medicine, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catharina","family":"Westphal","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Klinikum Rechts der Isar, Technical University of Munich School of Medicine, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Klug","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Klinikum Rechts der Isar, Technical University of Munich School of Medicine, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4903-0118","authenticated-orcid":false,"given":"Gerhard","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Klinikum Rechts der Isar, Technical University of Munich School of Medicine, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Kreuzer","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Klinikum Rechts der Isar, Technical University of Munich School of Medicine, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rainer","family":"Haseneder","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Klinikum Rechts der Isar, Technical University of Munich School of Medicine, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Kratzer","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Klinikum Rechts der Isar, Technical University of Munich School of Medicine, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1007\/s00101-013-2206-6","article-title":"Dexmedetomidin","volume":"62","author":"Gerresheim","year":"2013","journal-title":"Anaesthesist"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1007\/s40265-015-0419-5","article-title":"Dexmedetomidine: A Review of Its Use for Sedation in the Intensive Care Setting","volume":"75","author":"Keating","year":"2015","journal-title":"Drugs"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.1399-6576.2007.01537.x","article-title":"Electroencephalogram spindle activity during dexmedetomidine sedation and physiological sleep","volume":"52","author":"Huupponen","year":"2008","journal-title":"Acta Anaesthesiol. 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