{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T02:58:43Z","timestamp":1740106723336,"version":"3.37.3"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2022,8,9]],"date-time":"2022-08-09T00:00:00Z","timestamp":1660003200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100003725","name":"The National Research Foundation of Korea","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Korean Government","award":["2021-R1F1A1045544","2021-R1A4A1031574"],"award-info":[{"award-number":["2021-R1F1A1045544","2021-R1A4A1031574"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,9,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We investigated the effect of the acetylcholine muscarinic receptor inhibitor benztropine on voltage-dependent K+ (Kv) channels in rabbit coronary arterial smooth muscle cells. Benztropine inhibited Kv currents in a concentration-dependent manner, with an apparent IC50 value of 6.11\u2009\u00b1\u20090.80\u2009\u03bcM and Hill coefficient of 0.62\u2009\u00b1\u20090.03. Benztropine shifted the steady-state activation curves toward a more positive potential, and the steady-state inactivation curves toward a more negative potential, suggesting that benztropine inhibited Kv channels by affecting the channel voltage sensor. Train pulse (1 or 2\u2009Hz)-induced Kv currents were effectively reduced by the benztropine treatment. Furthermore, recovery time constants of Kv current inactivation increased significantly in response to benztropine. These results suggest that benztropine inhibited vascular Kv channels in a use (state)-dependent manner. The inhibitory effect of benztropine was canceled by pretreatment with the Kv 1.5 inhibitor, but there was no obvious change after pretreatment with Kv 2.1 or Kv7 inhibitors. In conclusion, benztropine inhibited the Kv current in a concentration- and use (state)-dependent manner. Inhibition of the Kv channels by benztropine primarily involved the Kv1.5 subtype. Restrictions are required when using benztropine to patients with vascular disease.<\/jats:p>","DOI":"10.1093\/toxsci\/kfac083","type":"journal-article","created":{"date-parts":[[2022,8,9]],"date-time":"2022-08-09T20:00:19Z","timestamp":1660075219000},"page":"260-267","source":"Crossref","is-referenced-by-count":1,"title":["Blockade of Voltage-Dependent K+ Channels by Benztropine, a Muscarinic Acetylcholine Receptor Inhibitor, in Coronary Arterial Smooth Muscle Cells"],"prefix":"10.1093","volume":"189","author":[{"given":"Minji","family":"Kang","sequence":"first","affiliation":[{"name":"Department of Physiology, Kangwon National University School of Medicine , Chuncheon 24341, South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin Ryeol","family":"An","sequence":"additional","affiliation":[{"name":"Department of Physiology, Kangwon National University School of Medicine , Chuncheon 24341, South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongliang","family":"Li","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Institute of Translational Medicine, Medical College, Yangzhou University , Yangzhou 225001, PR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenwen","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Institute of Translational Medicine, Medical College, Yangzhou University , Yangzhou 225001, PR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryeon","family":"Heo","sequence":"additional","affiliation":[{"name":"Department of Physiology, Kangwon National University School of Medicine , Chuncheon 24341, South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seojin","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Physiology, Kangwon National University School of Medicine , Chuncheon 24341, South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seo-Yeong","family":"Mun","sequence":"additional","affiliation":[{"name":"Department of Physiology, Kangwon National University School of Medicine , Chuncheon 24341, South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minju","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Physiology, Kangwon National University School of Medicine , Chuncheon 24341, South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mi Seon","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Physiology, Konkuk University School of Medicine , Chungju 27478, South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eun-Taek","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Medical Environmental Biology and Tropical Medicine, Kangwon National University School of Medicine , Chuncheon 24341, South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin-Hee","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Medical Environmental Biology and Tropical Medicine, Kangwon National University School of Medicine , Chuncheon 24341, South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanjoo","family":"Chun","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Kangwon National University School of Medicine , Chuncheon 24341, South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5868-3797","authenticated-orcid":false,"given":"Won Sun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Physiology, Kangwon National University School of Medicine , Chuncheon 24341, South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,8,9]]},"reference":[{"key":"2022092808033282900_kfac083-B1","doi-asserted-by":"crossref","first-page":"66","DOI":"10.2302\/kjm.61.66","article-title":"Anticholinergic syndrome and supraventricular tachycardia caused by lavender tea toxicity","volume":"61","author":"Acikalin","year":"2012","journal-title":"Keio J. 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