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Epilepsy: Molecular Neuropharmacology, Calcium Signalling, Neuroinflammation, and Drug Discovery

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: 31 May 2026 | Viewed by 641

Special Issue Editor


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Guest Editor
1. Departamento de Farmacología, Facultad de Medicina, Universidad Autónoma de Madrid, 28029 Madrid, Spain
2. Instituto de Investigaciones Biomédicas, Hospital Universitario de la Princesa, Diego de León 62, 28006 Madrid, Spain
Interests: Alzheimer's; amyotrophic lateral sclerosis; calcium signaling; pericam; aequorin; neuroprotection
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Special Issue Information

Dear Colleagues,

This Special Issue will focus on the molecular pharmacology of epilepsy, emphasizing receptor-mediated mechanisms that contribute to neuronal excitability, seizure initiation, and propagation. It aims to highlight advances in our understanding of neurotransmitter receptor modulation (e.g., GABAergic, glutamatergic, purinergic, nicotinic, and serotonergic systems), signal transduction pathways, and novel receptor targets with therapeutic potential.

Both original research and comprehensive reviews covering new pharmacological strategies, receptor-targeted drug development, and translational perspectives are welcome

Dr. Maria F. Cano-Abad
Guest Editor

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Keywords

  • epilepsy receptor pharmacology
  • neurotransmitter receptor modulation
  • calcium signaling and homeostasis
  • therapeutic targets in epilepsy
  • GABAergic and glutamatergic systems

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Published Papers (1 paper)

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Research

16 pages, 918 KB  
Article
Valproic Acid Stimulates Release of Ca2+ from InsP3-Sensitive Ca2+ Stores
by Ana Ruiz-Nuño and María F. Cano-Abad
Int. J. Mol. Sci. 2026, 27(3), 1176; https://doi.org/10.3390/ijms27031176 - 23 Jan 2026
Viewed by 451
Abstract
Calcium (Ca2+)signaling dysfunction is a central contributor to neuronal hyperexcitability and seizure propagation in epilepsy, yet the intracellular mechanisms underlying the actions of valproic acid (VPA) remain incompletely understood. In this study, we investigated whether VPA modulates Ca2+ homeostasis at [...] Read more.
Calcium (Ca2+)signaling dysfunction is a central contributor to neuronal hyperexcitability and seizure propagation in epilepsy, yet the intracellular mechanisms underlying the actions of valproic acid (VPA) remain incompletely understood. In this study, we investigated whether VPA modulates Ca2+ homeostasis at the level of the endoplasmic reticulum (ER) and how this action influences cytosolic Ca2+ dynamics associated with epileptiform activity. ER Ca2+ levels were directly measured using ER-targeted aequorin in HeLa and PC12 cells, while cytosolic Ca2+ signals were monitored by fura-2 fluorescence imaging in bovine chromaffin cells exposed to veratridine, a model of sustained sodium channel activation and Ca2+ oscillations. VPA induced a concentration-dependent release of Ca2+ from the ER, with an IC50 of approximately 17 µM. This effect was preserved in permeabilized cells and exhibited activation kinetics comparable to those elicited by inositol 1,4,5-trisphosphate (InsP3). Pharmacological inhibition of InsP3 receptors (InsP3Rs), but not ryanodine receptors or SERCA, abolished VPA-induced ER Ca2+ release, supporting a selective InsP3R-mediated mechanism. Functionally, VPA suppressed the repetitive cytosolic Ca2+ oscillations induced by veratridine, while simultaneously producing a sustained elevation of cytosolic Ca2+ originating from ER stores and facilitating depolarization-evoked catecholamine secretion. Together, these results support the conclusion that VPA induces InsP3R-mediated Ca2+ mobilization from the endoplasmic reticulum and identify ER Ca2+ release as a previously unrecognized intracellular mechanism contributing to its modulatory effects on Ca2+ signaling and excitability in epilepsy. Full article
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