{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T17:48:34Z","timestamp":1791827314082,"version":"4.3.4"},"reference-count":53,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,31]],"date-time":"2025-08-31T00:00:00Z","timestamp":1756598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science and Technology Council, Taiwan","award":["NSTC 114-2314-B-006-059-"],"award-info":[{"award-number":["NSTC 114-2314-B-006-059-"]}]},{"name":"National Science and Technology Council, Taiwan","award":["MOST-109-2314-B-006-033-MY3"],"award-info":[{"award-number":["MOST-109-2314-B-006-033-MY3"]}]},{"name":"National Science and Technology Council, Taiwan","award":["NSTC-112-2923-B-006-001"],"award-info":[{"award-number":["NSTC-112-2923-B-006-001"]}]},{"name":"National Science and Technology Council, Taiwan","award":["NCKUH-11402064"],"award-info":[{"award-number":["NCKUH-11402064"]}]},{"name":"National Science and Technology Council, Taiwan","award":["ANHRF-114-43"],"award-info":[{"award-number":["ANHRF-114-43"]}]},{"name":"National Science and Technology Council, Taiwan","award":["114-049"],"award-info":[{"award-number":["114-049"]}]},{"name":"National Chengkung hospital of national Chengkung University","award":["NSTC 114-2314-B-006-059-"],"award-info":[{"award-number":["NSTC 114-2314-B-006-059-"]}]},{"name":"National Chengkung hospital of national Chengkung University","award":["MOST-109-2314-B-006-033-MY3"],"award-info":[{"award-number":["MOST-109-2314-B-006-033-MY3"]}]},{"name":"National Chengkung hospital of national Chengkung University","award":["NSTC-112-2923-B-006-001"],"award-info":[{"award-number":["NSTC-112-2923-B-006-001"]}]},{"name":"National Chengkung hospital of national Chengkung University","award":["NCKUH-11402064"],"award-info":[{"award-number":["NCKUH-11402064"]}]},{"name":"National Chengkung hospital of national Chengkung University","award":["ANHRF-114-43"],"award-info":[{"award-number":["ANHRF-114-43"]}]},{"name":"National Chengkung hospital of national Chengkung University","award":["114-049"],"award-info":[{"award-number":["114-049"]}]},{"name":"An Nan Hospital, Tainan, Taiwan","award":["NSTC 114-2314-B-006-059-"],"award-info":[{"award-number":["NSTC 114-2314-B-006-059-"]}]},{"name":"An Nan Hospital, Tainan, Taiwan","award":["MOST-109-2314-B-006-033-MY3"],"award-info":[{"award-number":["MOST-109-2314-B-006-033-MY3"]}]},{"name":"An Nan Hospital, Tainan, Taiwan","award":["NSTC-112-2923-B-006-001"],"award-info":[{"award-number":["NSTC-112-2923-B-006-001"]}]},{"name":"An Nan Hospital, Tainan, Taiwan","award":["NCKUH-11402064"],"award-info":[{"award-number":["NCKUH-11402064"]}]},{"name":"An Nan Hospital, Tainan, Taiwan","award":["ANHRF-114-43"],"award-info":[{"award-number":["ANHRF-114-43"]}]},{"name":"An Nan Hospital, Tainan, Taiwan","award":["114-049"],"award-info":[{"award-number":["114-049"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>QX-314 is a positively charged lidocaine derivative with the membrane-impermeant property. This compound applied at the intracellular side has been shown to suppress the voltage-gated Na+ current (INa), while lidocaine itself acts to suppress the hyperpolarization-activated cation current (Ih). To what extent this drug may exert any effects on various plasmalemmal ionic currents still remains largely unknown. This investigation focused on the impact of QX-314 on ionic currents in GH3 cells derived from pituitary tumors. This compound applied extracellularly was noted to differentially suppress the amplitude of transient and late INa with an IC50 value of 93 and 42 \u03bcM, respectively. In GH3 cells dialyzed with QX-314 (10 \u03bcM), the INa(T) amplitude evoked by a brief depolarizing step was decreased, and its inactivation was increased. Moreover, QX-314, when applied extracellularly at 100 \u03bcM, diminished the amplitude of the Ih current with an IC50 of 68 \u03bcM. Intracellular dialysis with QX-314 also suppressed Ih amplitude; moreover, the later application of oxaliplatin reversed this suppression. As cells were extracellularly and continually exposed to QX-314, the magnitude of the erg-mediated K+ current (IK(erg)) was also effectively suppressed with an IC50 value of 73 \u03bcM. Furthermore, upon intracellular dialysis with QX-314 (10 \u03bcM), the degree of the voltage-dependent hysteresis (Hys(V)) of IK(erg) during the long-lasting isosceles-triangular ramp voltage was decreased; during continued exposure to QX-314, further extracellular bath additions of PD118057 (10 \u03bcM) counteracted QX-314-induced suppression. However, the extracellular addition of QX-314 (100 \u03bcM) mildly suppressed the outward delayed rectifier K+ current in GH3 cells. Collectively, QX-314 effectively suppressed INa, Ih, and IK(erg) in GH3 cells, a model of endocrine function, and these actions may contribute to their physiological functions, if similar effects are observed in vivo.<\/jats:p>","DOI":"10.3390\/ijms26178469","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T15:02:57Z","timestamp":1756825377000},"page":"8469","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Modulation of INa, Ih, and IK(erg) by Extracellular or Intracellular QX-314 (N-(2,6-dimethylphenylcarbamoylmethyl) triethylammonium bromide) in Pituitary Tumor Cells"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2795-0906","authenticated-orcid":false,"given":"Jeffrey Chi-Fei","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0836-707X","authenticated-orcid":false,"given":"Hung-Tsung","family":"Hsiao","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5208-3253","authenticated-orcid":false,"given":"Sheng-Nan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan"},{"name":"Department of Post-Baccalaureate Medicine, National Sun Yat-sen University Medical College, Kaohsiung 804, Taiwan"},{"name":"Department of Research and Education, An Nan Hospital, China Medical University, Tainan 70965, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1111\/j.1749-6632.1991.tb33842.x","article-title":"Voltage-sensitive sodium channels: Agents that perturb inactivation gating","volume":"625","author":"Agnew","year":"1991","journal-title":"Ann. 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