H3 Receptor Antagonism Reduces Macroscopic K+ Currents in a Voltage-Dependent Manner in Diabetic Rat DRG Neurons: Insights into Pain Regulation

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dc.contributor.authorAltinok, Feyza Alyu
dc.contributor.authorBoubekka, Abderaouf
dc.contributor.authorDallali, Ilhem
dc.contributor.authorHasan, Ahmed
dc.contributor.authorAcikgul, Muhammet Burak
dc.contributor.authorBurak, Yusuf
dc.contributor.authorOzturk, Yusuf
dc.date.accessioned2026-04-04T13:31:22Z
dc.date.available2026-04-04T13:31:22Z
dc.date.issued2025
dc.departmentİnönü Üniversitesi
dc.description.abstractBackground and aims: Diabetic neuropathy involves sensory neuron hyperexcitability. We examined how H3 receptor antagonism affects total K'currents in dorsal root ganglion (DRG) neurons from streptozocin-induced diabetic rats. Methods: Neuropathy was confirmed by e-von Frey and Hargreave's testing at 4 weeks post-injection. K+ currents were investigated using whole-cell patch-clamp recordings in the voltage-clamp mode. To activate the voltage-gated K+ channels, the neurons were held at-60 mV and subjected to a series of depolarising pulses from-60 mV up to +100 mV in 10 mV increments. Results: Acute application of thioperamide (100 & micro;M) significantly reduced K'currents in the depolarised voltage range of +30 to +100 mV, with p-values ranging from 0.0362 to 0.0031 (n = 13) and an increasing significance at higher voltages. In the conductance-voltage analysis, thioperamide was found to significantly alter the voltage dependence of channel activation, likely reducing the active channel numbers or their open probability. Conclusion: The voltage-dependent inhibition likely reflects the modulation of the high-voltage activated voltage-gated K' channels. The reduction in K' currents can be paradoxically interpreted: decreased K' conductance may enhance neuronal excitability by impairing repolarization but also prolong the action potential duration, potentially limiting immediate repetitive firing. Thioperamide increases histamine release by blocking H3 autoreceptor, reducing neuroinflammation and producing analgesia despite its possible excitatory effects on DRG neurons. This highlights the dual peripheral and central roles of H3 modulation in diabetic neuropathy. Future studies should explore the in vivo relevance of these ionic changes and their impact on pain behaviour.
dc.description.sponsorshipAnadolu University Scientific Research Foundation [AUBAP-2203S021]
dc.description.sponsorshipThis study was supported by the Anadolu University Scientific Research Foundation (AUBAP-2203S021, Eskisehir, Turkiye) .
dc.identifier.doi10.26650/IstanbulJPharm.2025.1704042
dc.identifier.endpage418
dc.identifier.issn2587-2087
dc.identifier.issue3
dc.identifier.orcid0000-0003-1025-3039
dc.identifier.startpage411
dc.identifier.urihttps://doi.org/10.26650/IstanbulJPharm.2025.1704042
dc.identifier.urihttps://hdl.handle.net/11616/108763
dc.identifier.volume55
dc.identifier.wosWOS:001693702300009
dc.identifier.wosqualityQ4
dc.indekslendigikaynakWeb of Science
dc.language.isoen
dc.publisherIstanbul Univ, Fac Pharmacy
dc.relation.ispartofIstanbul Journal of Pharmacy
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WOS_20250329
dc.subjectDiabetic Neuropathy
dc.subjectDorsal Root Ganglion Neurons
dc.subjectH-3 Receptor Antagonist
dc.subjectPatch-Clamp Technique
dc.subjectPotassium Currents
dc.titleH3 Receptor Antagonism Reduces Macroscopic K+ Currents in a Voltage-Dependent Manner in Diabetic Rat DRG Neurons: Insights into Pain Regulation
dc.typeArticle

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