{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:09:34Z","timestamp":1760234974187,"version":"build-2065373602"},"reference-count":52,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,7,4]],"date-time":"2021-07-04T00:00:00Z","timestamp":1625356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"An Nan Hospital, China Medical University","award":["ANHRF2019-03"],"award-info":[{"award-number":["ANHRF2019-03"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Midazolam (MDZ) could affect lymphocyte immune functions. However, the influence of MDZ on cell\u2019s K+ currents has never been investigated. Thus, in the present study, the effects of MDZ on Jurkat T lymphocytes were studied using the patch-clamp technique. Results showed that MDZ suppressed the amplitude of delayed-rectifier K+ current (IK(DR)) in concentration-, time-, and state-dependent manners. The IC50 for MDZ-mediated reduction of IK(DR) density was 5.87 \u03bcM. Increasing MDZ concentration raised the rate of current-density inactivation and its inhibitory action on IK(DR) density was estimated with a dissociation constant of 5.14 \u03bcM. In addition, the inactivation curve of IK(DR) associated with MDZ was shifted to a hyperpolarized potential with no change on the slope factor. MDZ-induced inhibition of IK(DR) was not reversed by flumazenil. In addition, the activity of intermediate-conductance Ca2+-activated K+ (IKCa) channels was suppressed by MDZ. Furthermore, inhibition by MDZ on both IK(DR) and IKCa-channel activity appeared to be independent from GABAA receptors and affected immune-regulating cytokine expression in LPS\/PMA-treated human T lymphocytes. In conclusion, MDZ suppressed current density of IK(DR) in concentration-, time-, and state-dependent manners in Jurkat T-lymphocytes and affected immune-regulating cytokine expression in LPS\/PMA-treated human T lymphocytes.<\/jats:p>","DOI":"10.3390\/ijms22137198","type":"journal-article","created":{"date-parts":[[2021,7,4]],"date-time":"2021-07-04T22:34:36Z","timestamp":1625438076000},"page":"7198","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Midazolam\u2019s Effects on Delayed-Rectifier K+ Current and Intermediate-Conductance Ca2+-Activated K+ Channel in Jurkat T-lymphocytes"],"prefix":"10.3390","volume":"22","author":[{"given":"Ning-Ping","family":"Foo","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine, An Nan Hospital, China Medical University, Tainan City 709204, Taiwan"},{"name":"Graduate Institute of Medical Sciences, Chang Jung Christian University, Tainan City 711301, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Fan","family":"Liu","sequence":"additional","affiliation":[{"name":"Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei City 100233, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping-Ching","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, National Cheng Kung University, Tainan City 70101, Taiwan"},{"name":"Institute of Oral Medicine and Department of Stomatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City 704302, Taiwan"},{"name":"Center of Applied Nanomedicine, National Cheng Kung University, Tainan City 70101, Taiwan"},{"name":"Medical Device Innovation Center, Taiwan Innovation Center of Medical Devices and Technology, National Cheng Kung University Hospital, National Cheng Kung University, Tainan City 704302, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chung-Hsi","family":"Hsing","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Chi Mei Medical Center, Tainan City 710402, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bu-Miin","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Anatomy, National Cheng Kung University, Tainan City 70101, Taiwan"},{"name":"Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404332, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2480-8843","authenticated-orcid":false,"given":"Edmund-Cheung","family":"So","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medical Sciences, Chang Jung Christian University, Tainan City 711301, Taiwan"},{"name":"Department of Anesthesia & Medical Research, An Nan Hospital, China Medical University, Tainan City 709204, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/s10753-011-9313-9","article-title":"The Burn Wound Inflammatory Response Is Influenced by Midazolam","volume":"35","author":"Babcock","year":"2011","journal-title":"Inflammation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1159\/000369277","article-title":"Diazepam Inhibits Proliferation of Lymph Node Cells Isolated from Rats with Experimental Autoimmune Encephalomyelitis","volume":"22","author":"Hurst","year":"2015","journal-title":"Neuroimmunomodulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1038\/jid.2010.245","article-title":"The Beneficial Effect of Blocking Kv1.3 in the Psoriasiform SCID Mouse Model","volume":"131","author":"Gilhar","year":"2011","journal-title":"J. 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