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This study used patch clamp recordings to test how TPM alters the amplitude, gating, and hysteresis of voltage-gated sodium current and the hyperpolarization-activated cation current in electrically excitable GH3 lactotrophs. TPM inhibited transient and late sodium components concentration-dependently, suppressed Ih density, slowed Ih activation, and reduced hysteretic strength, while TPM also suppressed spontaneous action potentials.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/dual-block-evidence-of-the-effects-of-topiramate-a-sulfamate-substituted-monosaccharide-on-voltage-gated-sodium-current-and-hyperpolarization-activated-cation-current/446372/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/dual-block-evidence-of-the-effects-of-topiramate-a-sulfamate-substituted-monosaccharide-on-voltage-gated-sodium-current-and-hyperpolarization-activated-cation-current/446372.png","ImageObject",300,407,{"name":92,"@type":93},"Đào","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-31","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":29},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What ionic currents were examined in the study?","Question",{"text":112,"@type":113},"The study examined voltage-gated sodium current components (transient INa(T) and late INa(L)) and the hyperpolarization-activated cation current (Ih).","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How did topiramate affect sodium current gating and amplitude?",{"text":117,"@type":113},"TPM produced concentration-dependent inhibition of both INa(T) and INa(L) components. 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BMC Pharmacology and Toxicology (2026) 27:4  \n[https://doi.org/10.1186/s40360-025-01043-6](https://doi.org/10.1186/s40360-025-01043-6)  \nBMC Pharmacology and Toxicology  \nRESEARCH Open Access  \nDual block evidence of the effects of topiramate, a sulfamate-substituted monosaccharide, on voltage-gated sodium current and hyperpolarization-activated cation current  \nRay-Chang Tzeng 1, Ming-Chi Lai2, Sheng-Nan Wu3,4* and Chin-Wei Huang5*  \nAbstract  \nBackground Topiramate (TPM) is a sulfamate-substituted monosaccharide known for its wide-ranging effects on epilepsy, neuropathic pain, and migraines. However, its precise influence on plasmalemmal ionic currents, including their magnitude and gating kinetics, remains uncertain. Therefore, a reassessment of the regulatory effect ofTPM on ionic currents in electrically excitable cells is warranted.  \nMethods With the aid of patch clamp technology, we investigated the effects ofTPM on the amplitude, gating, and hysteresis of plasmalemmal ionic currents from GH3 lactotrophs.  \nResults We observed that TPM exhibited a concentration-dependent inhibition of both transient (INa(T)) and late (INa(L)) components of INa, activated by brief depolarizing stimuli. At low concentration, TPM did not show any noticeable effect on INa(T); however, it was effective in reducing INa(L) amplitude. TPM caused a leftward shift in the midpoint of the steady-state inactivation curve of INa(T) without altering the gating charge. Importantly, the overall current density versus voltage relationship of INa(T) remained unaltered during TPM exposure. Intriguingly, the reduction in INa(T) induced by TPM could not be reversed by subsequent additions of flumazenil or chlorotoxin. Furthermore, TPM suppressed the density of the hyperpolarization-activated cation current (Ih). Simultaneously, the activation time course of Ih slowed in the presence ofTPM. Moreover, TPM exposure decreased the hysteretic strength activated by double triangular ramp voltage, a change partially reversed by oxal iplatin. In current-clamp potential recordings, spontaneous action potentials were susceptible to suppression in the presence ofTPM.  \nConclusions Collectively, these findings strongly suggest that TPM’s effects on INa and Ih have the potential to impact the functional activities and electrical behaviors of excitable cells.  \n*Correspondence:  \nSheng-Nan Wu [snwu@mail.ncku.edu.tw](snwu@mail.ncku.edu.tw)[ ](snwu@mail.ncku.edu.tw)Chin-Wei Huang [huangcw@mail.ncku.edu.tw](huangcw@mail.ncku.edu.tw)  \nFull list of author information is available at the end of the article  \n© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/l](http://creativecommons.org/l)icenses/by/4.0/.  \nTzeng et al. BMC Pharmacology and Toxicology (2026) 27:4 Page 2 of 14  \nKeywords Topiramate, Voltage-gated Na+ current, Late Na+ current, Transient Na+ current, Hyperpolarizationactivated cation current  \nBackground  \nTopiramate (TPM) is an oral or intravenous medication used to prevent or reduce epileptic seizures. It can be used alone or in combination with other therapies inneuropathic or migraine pain. This drug is a sulfamatesubstituted monosaccharide and several st","cbCaigI4b8BacxDy","https://ap.wps.com/l/cbCaigI4b8BacxDy","pdf",2275264,14,"English","# Abstract\n# Background\n# Methods\n# Results\n# Conclusions","[{\"question\":\"What ionic currents were examined in the study?\",\"answer\":\"The study examined voltage-gated sodium current components (transient INa(T) and late INa(L)) and the hyperpolarization-activated cation current (Ih).\"},{\"question\":\"How did topiramate affect sodium current gating and amplitude?\",\"answer\":\"TPM produced concentration-dependent inhibition of both INa(T) and INa(L) components. It reduced INa(L) amplitude and caused a leftward shift in the steady-state inactivation midpoint for INa(T) without changing gating charge.\"},{\"question\":\"What were the observed effects of topiramate on Ih and neuronal activity?\",\"answer\":\"TPM suppressed Ih density and slowed Ih activation time course. In current-clamp recordings, spontaneous action potentials were susceptible to suppression during TPM exposure.\"}]","Dual block evidence of the effects of topiramate, a sulfamate-substituted monosaccharide, on voltage-gated sodium current and hyperpolarization-activated cation current | PDF",1790715160,35]