{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:21:54Z","timestamp":1788456114589,"version":"build-2803163510"},"reference-count":44,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2018,7,4]],"date-time":"2018-07-04T00:00:00Z","timestamp":1530662400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2015R1D1A3A01017856"],"award-info":[{"award-number":["2015R1D1A3A01017856"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2015R1A-5A2-008833"],"award-info":[{"award-number":["2015R1A-5A2-008833"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tandem pore domain weak inward rectifier potassium channel (TWIK)-related spinal cord K+ (TRESK; K2P18.1) channel is the only member of the two-pore domain K+ (K2P) channel family that is activated by an increase in intracellular Ca2+ concentration ([Ca2+]i) and linked to migraines. This study was performed to identify the effect of verapamil, which is an L-type Ca2+ channel blocker and a prophylaxis for migraines, on the TRESK channel in trigeminal ganglion (TG) neurons, as well as in a heterologous system. Single-channel and whole-cell currents were recorded in TG neurons and HEK-293 cells transfected with mTRESK using patch-clamping techniques. In TG neurons, changes in [Ca2+]i were measured using the fluo-3-AM Ca2+ indicator. Verapamil, nifedipine, and NiCl2 inhibited the whole-cell currents in HEK-293 cells overexpressing mTRESK with IC50 values of 5.2, 54.3, and &gt;100 \u03bcM, respectively. The inhibitory effect of verapamil on TRESK channel was also observed in excised patches. In TG neurons, verapamil (10 \u03bcM) inhibited TRESK channel activity by approximately 76%. The TRESK channel activity was not dependent on the presence of extracellular Ca2+. In addition, the inhibitory effect of verapamil on the TRESK channel remained despite the absence of extracellular Ca2+. These findings show that verapamil inhibits the TRESK current independently of the blockade of Ca2+ influx in TG neurons. Verapamil will be able to exert its pharmacological effects by modulating TRESK, as well as Ca2+ influx, in TG neurons in vitro. We suggest that verapamil could be used as an inhibitor for identifying TRESK channel in TG neurons.<\/jats:p>","DOI":"10.3390\/ijms19071961","type":"journal-article","created":{"date-parts":[[2018,7,4]],"date-time":"2018-07-04T12:23:02Z","timestamp":1530706982000},"page":"1961","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Verapamil Inhibits TRESK (K2P18.1) Current in Trigeminal Ganglion Neurons Independently of the Blockade of Ca2+ Influx"],"prefix":"10.3390","volume":"19","author":[{"given":"Hyun","family":"Park","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, College of Medicine and Institute of Health Sciences, Gyeongsang National University, Jinju 52727, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun-Jin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Physiology and Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji","family":"Ryu","sequence":"additional","affiliation":[{"name":"Department of Physiology and Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, South Korea"},{"name":"Department of Convergence Medical Science, Gyeongsang National University, Jinju 52727, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9969-0117","authenticated-orcid":false,"given":"Dong","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Physiology and Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, South Korea"},{"name":"Department of Convergence Medical Science, Gyeongsang National University, Jinju 52727, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong-Geun","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Physiology and Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, South Korea"},{"name":"Department of Convergence Medical Science, Gyeongsang National University, Jinju 52727, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaehee","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Physiology and Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jongwoo","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, College of Medicine and Institute of Health Sciences, Gyeongsang National University, Jinju 52727, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7402-7298","authenticated-orcid":false,"given":"Dawon","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, South Korea"},{"name":"Department of Convergence Medical Science, Gyeongsang National University, Jinju 52727, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,7,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"18550","DOI":"10.1074\/jbc.M312229200","article-title":"The two-pore domain K+ channel, TRESK, is activated by the cytoplasmic calcium signal through calcineurin","volume":"279","author":"Czirjak","year":"2004","journal-title":"J. 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