{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:48:55Z","timestamp":1790189335270,"version":"4.1.0"},"reference-count":80,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2022,7,17]],"date-time":"2022-07-17T00:00:00Z","timestamp":1658016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Cheng Kung University Hospital","award":["NCKUH-11102050"],"award-info":[{"award-number":["NCKUH-11102050"]}]},{"name":"National Cheng Kung University Hospital","award":["NCKUH-11102029"],"award-info":[{"award-number":["NCKUH-11102029"]}]},{"name":"National Cheng Kung University Hospital","award":["MOST-110-2320-B-006-028"],"award-info":[{"award-number":["MOST-110-2320-B-006-028"]}]},{"name":"National Cheng Kung University Hospital","award":["110-2314-B-006-056"],"award-info":[{"award-number":["110-2314-B-006-056"]}]},{"name":"Ministry of Science and Technology","award":["NCKUH-11102050"],"award-info":[{"award-number":["NCKUH-11102050"]}]},{"name":"Ministry of Science and Technology","award":["NCKUH-11102029"],"award-info":[{"award-number":["NCKUH-11102029"]}]},{"name":"Ministry of Science and Technology","award":["MOST-110-2320-B-006-028"],"award-info":[{"award-number":["MOST-110-2320-B-006-028"]}]},{"name":"Ministry of Science and Technology","award":["110-2314-B-006-056"],"award-info":[{"award-number":["110-2314-B-006-056"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Carbamazepine (CBZ, Tegretol\u00ae) is an anticonvulsant used in the treatment of epilepsy and neuropathic pain; however, several unwanted effects of this drug have been noticed. Therefore, the regulatory actions of CBZ on ionic currents in electrically excitable cells need to be reappraised, although its efficacy in suppressing voltage-gated Na+ current (INa) has been disclosed. This study was undertaken to explore the modifications produced by CBZ on ionic currents (e.g., INa and erg-mediated K+ current [IK(erg)]) measured from Neuro-2a (N2a) cells. In these cells, we found that this drug differentially suppressed the peak (transient, INa(T)) and sustained (late, INa(L)) components of INa in a concentration-dependent manner with effective IC50 of 56 and 18 \u03bcM, respectively. The overall current\u2013voltage relationship of INa(T) with or without the addition of CBZ remained unchanged; however, the strength (i.e., \u2206area) in the window component of INa (INa(W)) evoked by the short ascending ramp pulse (Vramp) was overly lessened in the CBZ presence. Tefluthrin (Tef), a synthetic pyrethroid, known to stimulate INa, augmented the strength of the voltage-dependent hysteresis (Hys(V)) of persistent INa (INa(P)) in response to the isosceles-triangular Vramp; moreover, further application of CBZ attenuated Tef-mediated accentuation of INa(P)\u2019s Hys(V). With a two-step voltage protocol, the recovery of INa(T) inactivation seen in Neuro-2a cells became progressively slowed by adding CBZ; however, the cumulative inhibition of INa(T) evoked by pulse train stimulation was enhanced during exposure to this drug. Neuro-2a-cell exposure to CBZ (100 \u03bcM), the magnitude of erg-mediated K+ current measured throughout the entire voltage-clamp steps applied was mildly inhibited. The docking results regarding the interaction of CBZ and voltage-gate Na+ (NaV) channel predicted the ability of CBZ to bind to some amino-acid residues in NaV due to the existence of a hydrogen bond or hydrophobic contact. It is conceivable from the current investigations that the INa (INa(T), INa(L), INa(W), and INa(P)) residing in Neuro-2a cells are susceptible to being suppressed by CBZ, and that its block on INa(L) is larger than that on INa(T). Collectively, the magnitude and gating of NaV channels produced by the CBZ presence might have an impact on its anticonvulsant and analgesic effects occurring in vivo.<\/jats:p>","DOI":"10.3390\/ijms23147892","type":"journal-article","created":{"date-parts":[[2022,7,17]],"date-time":"2022-07-17T22:57:06Z","timestamp":1658098626000},"page":"7892","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Characterization in Inhibitory Effectiveness of Carbamazepine in Voltage-Gated Na+ and Erg-Mediated K+ Currents in a Mouse Neural Crest-Derived (Neuro-2a) Cell Line"],"prefix":"10.3390","volume":"23","author":[{"given":"Po-Ming","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"},{"name":"Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsin-Yen","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Physiology, National Cheng Kung University Medical College, Tainan 70101, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Wu","family":"Chiang","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzu-Hsien","family":"Chuang","sequence":"additional","affiliation":[{"name":"Department of Physiology, National Cheng Kung University Medical College, Tainan 70101, 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, National Cheng Kung University Medical College, Tainan 70101, Taiwan"},{"name":"Institute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan 70101, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9498-6178","authenticated-orcid":false,"given":"Yi-Fang","family":"Tu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"},{"name":"Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1007\/s40263-017-0441-0","article-title":"Sodium Channel Blockers in the Treatment of Epilepsy","volume":"31","author":"Brodie","year":"2017","journal-title":"CNS Drugs"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"109","DOI":"10.2174\/1570159X17666191010094350","article-title":"Trigeminal Neuralgia: Basic and Clinical Aspects","volume":"18","author":"Araya","year":"2020","journal-title":"Curr. Neuropharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1016\/S1474-4422(20)30233-7","article-title":"Advances in diagnosis, classification, pathophysiology, and management of trigeminal neuralgia","volume":"19","author":"Bendtsen","year":"2020","journal-title":"Lancet Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"107966","DOI":"10.1016\/j.neuropharm.2020.107966","article-title":"Mechanisms of action of currently used antiseizure drugs","volume":"168","author":"Sills","year":"2020","journal-title":"Neuropharmacology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"231.e3","DOI":"10.1016\/j.ajem.2022.01.044","article-title":"Neurologic toxicity of carbamazepine in treatment of trigeminal neuralgia","volume":"55","author":"Bridwell","year":"2022","journal-title":"Am. J. Emerg. Med."},{"key":"ref_6","first-page":"Cd001258","article-title":"Carbamazepine for schizophrenia","volume":"2014","author":"Leucht","year":"2014","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1007\/s11940-020-00644-2","article-title":"Treatment Updates for Neuromuscular Channelopathies","volume":"22","author":"Jitpimolmard","year":"2020","journal-title":"Curr. Treat. Options Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Grunze, A., Amann, B.L., and Grunze, H. (2021). Efficacy of Carbamazepine and Its Derivatives in the Treatment of Bipolar Disorder. Medicina, 57.","DOI":"10.3390\/medicina57050433"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e328","DOI":"10.1212\/WNL.0000000000013010","article-title":"Teaching Video NeuroImage: Carbamazepine Improves Gait Initiation in Autosomal Recessive Myotonia Congenita","volume":"98","author":"Fuseya","year":"2022","journal-title":"Neurology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e12763","DOI":"10.1111\/nan.12763","article-title":"The autophagy-enhancing drug carbamazepine improves neuropathology and motor impairment in mouse models of Machado-Joseph disease","volume":"48","author":"Silva","year":"2022","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1176\/ajp.145.10.1323-a","article-title":"Carbamazepine and hyponatremia","volume":"145","author":"Vieweg","year":"1988","journal-title":"Am. J. Psychiatry"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1176\/ajp.145.3.339","article-title":"Carbamazepine and hyponatremia in patients with affective disorder","volume":"145","author":"Yassa","year":"1988","journal-title":"Am. J. Psychiatry"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/0278-5846(94)90055-8","article-title":"Review of carbamazepine-induced hyponatremia","volume":"18","author":"Gandelman","year":"1994","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1111\/j.1528-1157.1994.tb02930.x","article-title":"Hyponatremia associated with carbamazepine and oxcarbazepine therapy: A review","volume":"35","author":"Bakshi","year":"1994","journal-title":"Epilepsia"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1046\/j.1365-2788.2001.00338.x","article-title":"Hyponatremia during carbamazepine therapy in patients with intellectual disability","volume":"45","author":"Kelly","year":"2001","journal-title":"J. Intellect. Disabil. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1976","DOI":"10.1212\/01.wnl.0000188819.45330.90","article-title":"Hyponatremia from oxcarbazepine and carbamazepine","volume":"65","author":"Dong","year":"2005","journal-title":"Neurology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.pediatrneurol.2006.01.011","article-title":"Carbamazepine-induced transient auditory pitch-perception deficit","volume":"35","author":"Tateno","year":"2006","journal-title":"Pediatr. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1080\/15622970600960157","article-title":"Hyponatremia-induced seizure during carbamazepine treatment","volume":"8","author":"Soyka","year":"2007","journal-title":"World J. Biol. Psychiatry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1111\/ene.13069","article-title":"Epidemiology, pathophysiology and putative genetic basis of carbamazepine- and oxcarbazepine-induced hyponatremia","volume":"23","author":"Berghuis","year":"2016","journal-title":"Eur. J. Neurol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1111\/epi.13777","article-title":"Carbamazepine- and oxcarbazepine-induced hyponatremia in people with epilepsy","volume":"58","author":"Berghuis","year":"2017","journal-title":"Epilepsia"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1111\/epi.16828","article-title":"Symptomatology of carbamazepine- and oxcarbazepine-induced hyponatremia in people with epilepsy","volume":"62","author":"Berghuis","year":"2021","journal-title":"Epilepsia"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.eplepsyres.2018.03.023","article-title":"Antiepileptic drugs-induced hyponatremia: Review and analysis of 560 hospitalized patients","volume":"143","author":"Intravooth","year":"2018","journal-title":"Epilepsy Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1186\/s13256-018-1744-6","article-title":"Walking hyponatremia syndrome of inappropriate antidiuretic hormone secretion secondary to carbamazepine use: A case report","volume":"12","author":"Pineda","year":"2018","journal-title":"J. Med. Case Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.4103\/jfmpc.jfmpc_185_19","article-title":"Carbamazepine-induced hyponatremia\u2014A wakeup call","volume":"8","author":"Kaeley","year":"2019","journal-title":"J. Family Med. Prim. Care"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"121","DOI":"10.18071\/isz.73.0121","article-title":"Effects of valproate, carbamazepine and levetiracetam on Tp-e interval, Tp-e\/QT and Tp-e\/QTc ratio","volume":"73","author":"Altun","year":"2020","journal-title":"Ideggyogy Sz"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Aso\u011flu, R., \u00d6zdemir, M., Alada\u011f, N., and Aso\u011flu, E. (2020). Evaluation of Cardiac Repolarization Indices in Epilepsy Patients Treated with Carbamazepine and Valproic Acid. Medicina, 56.","DOI":"10.3390\/medicina56010020"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"797039","DOI":"10.3389\/fphys.2021.797039","article-title":"The Role of Vasopressin V2 Receptor in Drug-Induced Hyponatremia","volume":"12","author":"Kim","year":"2021","journal-title":"Front. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"239","DOI":"10.2147\/NDT.S287042","article-title":"Effects of Antipsychotics on Arrhythmogenic Parameters in Schizophrenia Patients: Beyond Corrected QT Interval","volume":"17","author":"Okayasu","year":"2021","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"20942","DOI":"10.1074\/jbc.M113.470948","article-title":"Carbamazepine as a novel small molecule corrector of trafficking-impaired ATP-sensitive potassium channels identified in congenital hyperinsulinism","volume":"288","author":"Chen","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"101904","DOI":"10.1016\/j.jbc.2022.101904","article-title":"Carbamazepine promotes surface expression of mutant Kir6.2-A28V ATP-sensitive potassium channels by modulating Golgi retention and autophagy","volume":"298","author":"Lin","year":"2022","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Ding, Q., Zhang, F., Feng, Y., and Wang, H. (2020). Carbamazepine Restores Neuronal Signaling, Protein Synthesis, and Cognitive Function in a Mouse Model of Fragile X Syndrome. Int. J. Mol. Sci., 21.","DOI":"10.1101\/2020.01.07.897835"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1111\/j.1745-7254.2006.00452.x","article-title":"Kinetic changes and modulation by carbamazepine on voltage-gated sodium channels in rat CA1 neurons after epilepsy","volume":"27","author":"Sun","year":"2006","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1124\/mol.111.072751","article-title":"Inhibition of Nav\u03b24 peptide-mediated resurgent sodium currents in Nav1.7 channels by carbamazepine, riluzole, and anandamide","volume":"80","author":"Theile","year":"2011","journal-title":"Mol. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1124\/mol.113.090472","article-title":"Sidedness of carbamazepine accessibility to voltage-gated sodium channels","volume":"85","author":"Jo","year":"2014","journal-title":"Mol. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1111\/epi.13474","article-title":"The antiepileptic medications carbamazepine and phenytoin inhibit native sodium currents in murine osteoblasts","volume":"57","author":"Petty","year":"2016","journal-title":"Epilepsia"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1124\/pr.57.4.4","article-title":"International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels","volume":"57","author":"Catterall","year":"2005","journal-title":"Pharmacol. Rev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1016\/j.jtbi.2009.05.003","article-title":"Analytical studies of rapidly inactivating and noninactivating sodium currents in differentiated NG108-15 neuronal cells","volume":"259","author":"Wu","year":"2009","journal-title":"J. Theor. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Chang, W.T., and Wu, S.N. (2021). Characterization of Direct Perturbations on Voltage-Gated Sodium Current by Esaxerenone, a Nonsteroidal Mineralocorticoid Receptor Blocker. Biomedicines, 9.","DOI":"10.3390\/biomedicines9050549"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1254\/jphs.09018FP","article-title":"Effects of ranolazine, a novel anti-anginal drug, on ion currents and membrane potential in pituitary tumor GH(3) cells and NG108-15 neuronal cells","volume":"110","author":"Chen","year":"2009","journal-title":"J. Pharmacol. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1111\/pme.12681","article-title":"Reversal by ranolazine of doxorubicin-induced prolongation in the inactivation of late sodium current in rat dorsal root ganglion neurons","volume":"16","author":"Wu","year":"2015","journal-title":"Pain Med."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Chuang, T.H., Cho, H.Y., and Wu, S.N. (2021). The Evidence for Sparsentan-Mediated Inhibition of I(Na) and I(K(erg)): Possibly Unlinked to Its Antagonism of Angiotensin II or Endothelin Type a Receptor. Biomedicines, 10.","DOI":"10.3390\/biomedicines10010086"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Cho, H.Y., Chen, P.C., Chuang, T.H., Yu, M.C., and Wu, S.N. (2022). Activation of Voltage-Gated Na(+) Current by GV-58, a Known Activator of Ca(V) Channels. Biomedicines, 10.","DOI":"10.3390\/biomedicines10030721"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.tox.2009.01.009","article-title":"Underlying mechanism of actions of tefluthrin, a pyrethroid insecticide, on voltage-gated ion currents and on action currents in pituitary tumor (GH3) cells and GnRH-secreting (GT1-7) neurons","volume":"258","author":"Wu","year":"2009","journal-title":"Toxicology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.pestbp.2011.06.001","article-title":"Actions of Tefluthrin on Rat Na(v)1.7 Voltage-Gated Sodium Channels Expressed in Xenopus Oocytes","volume":"101","author":"Tan","year":"2011","journal-title":"Pestic. Biochem. Physiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.toxlet.2018.01.002","article-title":"Differential regulation of tefluthrin and telmisartan on the gating charges of I(Na) activation and inactivation as well as on resurgent and persistent I(Na) in a pituitary cell line (GH(3))","volume":"285","author":"So","year":"2018","journal-title":"Toxicol. Lett."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1113\/jphysiol.2005.097220","article-title":"Fibroblast growth factor 14 is an intracellular modulator of voltage-gated sodium channels","volume":"569","author":"Lou","year":"2005","journal-title":"J. Physiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e67914","DOI":"10.7554\/eLife.67914","article-title":"Enhanced excitability of cortical neurons in low-divalent solutions is primarily mediated by altered voltage-dependence of voltage-gated sodium channels","volume":"10","author":"Martiszus","year":"2021","journal-title":"eLife"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Wu, C.L., Chuang, C.W., Cho, H.Y., Chuang, T.H., and Wu, S.N. (2022). The Evidence for Effective Inhibition of I(Na) Produced by Mirogabalin ((1R,5S,6S)-6-(aminomethyl)-3-ethyl-bicyclo [3.2.0] hept-3-ene-6-acetic acid), a Known Blocker of Ca(V) Channels. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23073845"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Chang, W.T., and Wu, S.N. (2021). Effectiveness of Columbianadin, a Bioactive Coumarin Derivative, in Perturbing Transient and Persistent I(Na). Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22020621"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"19","DOI":"10.3389\/fphar.2012.00019","article-title":"Left-shifted nav channels in injured bilayer: Primary targets for neuroprotective nav antagonists?","volume":"3","author":"Morris","year":"2012","journal-title":"Front. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1002\/neu.20050","article-title":"Background sodium current stabilizes bursting in respiratory pacemaker neurons","volume":"60","author":"Tryba","year":"2004","journal-title":"J. Neurobiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2423","DOI":"10.1111\/j.1460-9568.2008.06537.x","article-title":"Background sodium current underlying respiratory rhythm regularity","volume":"28","author":"Chevalier","year":"2008","journal-title":"Eur. J. Neurosci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"19","DOI":"10.4077\/CJP.2011.AMM002","article-title":"Contribution of non-inactivating Na+ current induced by oxidizing agents to the firing behavior of neuronal action potentials: Experimental and theoretical studies from NG108-15 neuronal cells","volume":"54","author":"Wu","year":"2011","journal-title":"Chin. J. Physiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"7401","DOI":"10.1523\/JNEUROSCI.0143-10.2010","article-title":"Pacemaking in dopaminergic ventral tegmental area neurons: Depolarizing drive from background and voltage-dependent sodium conductances","volume":"30","author":"Khaliq","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"100947","DOI":"10.1016\/j.yfrne.2021.100947","article-title":"Sodium background currents in endocrine\/neuroendocrine cells: Towards unraveling channel identity and contribution in hormone secretion","volume":"63","author":"Monteil","year":"2021","journal-title":"Front. Neuroendocrinol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/S0896-6273(02)00574-3","article-title":"Subthreshold sodium current from rapidly inactivating sodium channels drives spontaneous firing of tuberomammillary neurons","volume":"33","author":"Taddese","year":"2002","journal-title":"Neuron"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"066007","DOI":"10.1088\/1741-2560\/8\/6\/066007","article-title":"Frequency-dependent reduction of voltage-gated sodium current modulates retinal ganglion cell response rate to electrical stimulation","volume":"8","author":"Tsai","year":"2011","journal-title":"J. Neural. Eng."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e54940","DOI":"10.7554\/eLife.54940","article-title":"Sodium channels implement a molecular leaky integrator that detects action potentials and regulates neuronal firing","volume":"9","author":"Navarro","year":"2020","journal-title":"eLife"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1111\/j.1582-4934.2004.tb00256.x","article-title":"Functions of erg K+ channels in excitable cells","volume":"8","author":"Schwarz","year":"2004","journal-title":"J. Cell Mol. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1111\/1440-1681.12943","article-title":"Activation of voltage-gated sodium current and inhibition of erg-mediated potassium current caused by telmisartan, an antagonist of angiotensin II type-1 receptor, in HL-1 atrial cardiomyocytes","volume":"45","author":"Chang","year":"2018","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Chen, L., Cho, H.Y., Chuang, T.H., Ke, T.L., and Wu, S.N. (2022). The Effectiveness of Isoplumbagin and Plumbagin in Regulating Amplitude, Gating Kinetics, and Voltage-Dependent Hysteresis of erg-mediated K(+) Currents. Biomedicines, 10.","DOI":"10.3390\/biomedicines10040780"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2374","DOI":"10.1159\/000492653","article-title":"Evidence of Decreased Activity in Intermediate-Conductance Calcium-Activated Potassium Channels During Retinoic Acid-Induced Differentiation in Motor Neuron-Like NSC-34 Cells","volume":"48","author":"Chen","year":"2018","journal-title":"Cell Physiol. Biochem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.tiv.2015.10.001","article-title":"Exploration of new functional endpoints in neuro-2a cells for the detection of the marine biotoxins saxitoxin, palytoxin and tetrodotoxin","volume":"30","author":"Nicolas","year":"2015","journal-title":"Toxicol. In Vitro"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2831","DOI":"10.1007\/s12035-016-9871-9","article-title":"Epigenetic Downregulation of Scn3a Expression by Valproate: A Possible Role in Its Anticonvulsant Activity","volume":"54","author":"Tan","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1016\/j.bmcl.2017.01.054","article-title":"Inhibition of veratridine-induced delayed inactivation of the voltage-sensitive sodium channel by synthetic analogs of crambescin B","volume":"27","author":"Tsukamoto","year":"2017","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_66","first-page":"297","article-title":"Vitex negundo induces an anticonvulsant effect by inhibiting voltage gated sodium channels in murine Neuro 2A cell line","volume":"31","author":"Khan","year":"2018","journal-title":"Pak. J. Pharm. Sci."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Chuang, T.H., Cho, H.Y., and Wu, S.N. (2021). Effective Accentuation of Voltage-Gated Sodium Current Caused by Apocynin (4\u2032-Hydroxy-3\u2032-methoxyacetophenone), a Known NADPH-Oxidase Inhibitor. Biomedicines, 9.","DOI":"10.3390\/biomedicines9091146"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"579596","DOI":"10.3389\/fphar.2020.579596","article-title":"Hysteretic Behavior in Voltage-Gated Channels","volume":"11","author":"Chiem","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/BF03190248","article-title":"Pharmacokinetics of carbamazepine derived from a new tablet formulation","volume":"20","author":"Mikov","year":"1995","journal-title":"Eur. J. Drug Metab. Pharmacokinet."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1111\/epi.16293","article-title":"The pharmacokinetics of oral carbamazepine in rats dosed using an automated drug delivery system","volume":"60","author":"Hill","year":"2019","journal-title":"Epilepsia"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/0922-4106(91)90111-T","article-title":"Carbamazepine distinguishes between adenosine receptors that mediate different second messenger responses","volume":"206","author":"Steber","year":"1991","journal-title":"Eur. J. Pharmacol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1016\/j.molcel.2020.12.048","article-title":"A tamoxifen receptor within a voltage-gated sodium channel","volume":"81","author":"Sula","year":"2021","journal-title":"Mol. Cell"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/S1474-4422(10)70059-4","article-title":"Voltage-gated sodium channels as therapeutic targets in epilepsy and other neurological disorders","volume":"9","author":"Mantegazza","year":"2010","journal-title":"Lancet Neurol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/j.tips.2016.05.002","article-title":"Voltage-Gated Ion Channels in the PNS: Novel Therapies for Neuropathic Pain?","volume":"37","author":"Tibbs","year":"2016","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"554","DOI":"10.2175\/106143012X13373550427273","article-title":"Carbamazepine degradation by photolysis and titanium dioxide photocatalysis","volume":"84","author":"Im","year":"2012","journal-title":"Water Environ. Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"132505","DOI":"10.1016\/j.chemosphere.2021.132505","article-title":"Insights into the wavelength-dependent photolysis of chlorite: Elimination of carbamazepine and formation of chlorate","volume":"288","author":"Wang","year":"2022","journal-title":"Chemosphere"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1073\/pnas.65.1.129","article-title":"Isolation of microtubule protein from cultured mouse neuroblastoma cells","volume":"65","author":"Olmsted","year":"1970","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.jneumeth.2009.11.004","article-title":"Differentiation of mouse Neuro 2A cells into dopamine neurons","volume":"186","author":"Tremblay","year":"2010","journal-title":"J. Neurosci. Methods"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1111\/j.1476-5381.2012.02004.x","article-title":"Mechanism and molecular basis for the sodium channel subtype specificity of \u00b5-conopeptide CnIIIC","volume":"167","author":"Markgraf","year":"2012","journal-title":"Br. J. Pharmacol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1161\/STROKEAHA.111.000719","article-title":"Human umbilical vein endothelial cells protect against hypoxic-ischemic damage in neonatal brain via stromal cell-derived factor 1\/C-X-C chemokine receptor type 4","volume":"44","author":"Wu","year":"2013","journal-title":"Stroke"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/14\/7892\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:52:37Z","timestamp":1760140357000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/14\/7892"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,17]]},"references-count":80,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["ijms23147892"],"URL":"https:\/\/doi.org\/10.3390\/ijms23147892","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,17]]}}}