{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T01:22:56Z","timestamp":1777598576235,"version":"3.51.4"},"reference-count":67,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T00:00:00Z","timestamp":1648684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["MOST-110-2320-B-006-028"],"award-info":[{"award-number":["MOST-110-2320-B-006-028"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mirogabalin (MGB, Tarlige\u00ae), an inhibitor of the \u03b12\u03b4-1 subunit of voltage-gated Ca2+ (CaV) channels, is used as a way to alleviate peripheral neuropathic pain and diabetic neuropathy. However, to what extent MGB modifies the magnitude, gating, and\/or hysteresis of various types of plasmalemmal ionic currents remains largely unexplored. In pituitary tumor (GH3) cells, we found that MGB was effective at suppressing the peak (transient, INa(T)) and sustained (late, INa(L)) components of the voltage-gated Na+ current (INa) in a concentration-dependent manner, with an effective IC50 of 19.5 and 7.3 \u03bcM, respectively, while the KD value calculated on the basis of minimum reaction scheme was 8.2 \u03bcM. The recovery of INa(T) inactivation slowed in the presence of MGB, although the overall current\u2013voltage relation of INa(T) was unaltered; however, there was a leftward shift in the inactivation curve of the current. The magnitude of the window (INa(W)) or resurgent INa (INa(R)) evoked by the respective ascending or descending ramp pulse (Vramp) was reduced during cell exposure to MGB. MGB-induced attenuation in INa(W) or INa(R) was reversed by the further addition of tefluthrin, a pyrethroid insecticide known to stimulate INa. MGB also effectively lessened the strength of voltage-dependent hysteresis of persistent INa in response to the isosceles triangular Vramp. The cumulative inhibition of INa(T), evoked by pulse train stimulation, was enhanced in its presence. Taken together, in addition to the inhibition of CaV channels, the NaV channel attenuation produced by MGB might have an impact in its analgesic effects occurring in vivo.<\/jats:p>","DOI":"10.3390\/ijms23073845","type":"journal-article","created":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T21:34:29Z","timestamp":1648762469000},"page":"3845","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["The Evidence for Effective Inhibition of INa Produced by Mirogabalin ((1R,5S,6S)-6-(aminomethyl)-3-ethyl-bicyclo [3.2.0] hept-3-ene-6-acetic acid), a Known Blocker of CaV Channels"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7821-9406","authenticated-orcid":false,"given":"Chao-Liang","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Medical Research, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi City 60002, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao-Wei","family":"Chuang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi City 60002, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsin-Yen","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Physiology, National Cheng Kung University Medical College, Tainan City 70101, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tzu-Hsien","family":"Chuang","sequence":"additional","affiliation":[{"name":"Department of Physiology, National Cheng Kung University Medical College, Tainan City 70101, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5208-3253","authenticated-orcid":false,"given":"Sheng-Nan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Physiology, National Cheng Kung University Medical College, Tainan City 70101, Taiwan"},{"name":"Institute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan City 70101, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1080\/14737175.2016.1202764","article-title":"Alpha2delta ligands, gabapentin, pregabalin and mirogabalin: A review of their clinical pharmacology and therapeutic use","volume":"16","author":"Calandre","year":"2016","journal-title":"Expert Rev. 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