Academic Journal
EA1-linked Kv1.1 dysfunction enhances susceptibility to cerebellar spreading depression and a transient cerebellar refractory state.
| Τίτλος: | EA1-linked Kv1.1 dysfunction enhances susceptibility to cerebellar spreading depression and a transient cerebellar refractory state. |
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| Συγγραφείς: | Servettini I; Department of Medicine and Health Science 'V. Tiberio', University of Molise, Campobasso, Italy; Department of Medicine and Surgery, University of Perugia, 06156, Perugia, Italy. Electronic address: ilenio.servettini@unimol.it., Megaro A; Department of Medicine and Surgery, University of Perugia, 06156, Perugia, Italy., Caramia M; Center for Synaptic Neuroscience and Technology, Istituto Italiano di Tecnologia, Largo Rosanna Benzi 10, 16132, Genova, Italy; Department of Chemistry, Biology and Biotechnology, University of Perugia, Italy., Sforna L; Department of Chemistry, Biology and Biotechnology, University of Perugia, Italy., Michelucci A; Department of Chemistry, Biology and Biotechnology, University of Perugia, Italy., Catacuzzeno L; Department of Chemistry, Biology and Biotechnology, University of Perugia, Italy. Electronic address: luigi.catacuzzeno@unipg.it. |
| Πηγή: | Biochimica et biophysica acta. Molecular basis of disease [Biochim Biophys Acta Mol Basis Dis] 2026 Oct; Vol. 1872 (7), pp. 168302. Date of Electronic Publication: 2026 May 25. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 101731730 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-260X (Electronic) Linking ISSN: 09254439 NLM ISO Abbreviation: Biochim Biophys Acta Mol Basis Dis Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Amsterdam : Elsevier |
| Ιατρικοί όροι (MeSH): | Kv1.1 Potassium Channel*/genetics , Kv1.1 Potassium Channel*/metabolism , Cerebellum*/metabolism , Cerebellum*/pathology , Cerebellum*/physiopathology , Ataxia*/genetics , Ataxia*/metabolism , Ataxia*/pathology , Ataxia*/physiopathology , Cortical Spreading Depression*, Animals ; Mice ; Humans ; Male ; Mice, Inbred C57BL ; Female ; Myokymia |
| Περίληψη: | Episodic ataxia type 1 (EA1) is a neurological channelopathy caused by loss-of-function mutations in the KCNA1 gene, which encodes the Kv1.1 α-subunit of voltage-gated potassium channels. Clinically, EA1 is characterized by interictal myokymia and transient episodes of generalized ataxia. While the molecular basis of the disease is well established, the mechanisms underlying the paroxysmal nature of attacks remains unclear. Drawing parallels with migraine with aura, an episodic disorder in which cortical spreading depression (CSD), a propagating wave of neuronal and glial depolarization followed by prolonged suppression of excitability, triggers symptoms, we hypothesized that EA1 may similarly involve an increased susceptibility to cerebellar spreading depression (CeSD), driven by reduced Kv1.1 channel activity and heightened cerebellar excitability. In mouse cerebellar slices exposed to elevated extracellular K+, CeSD displayed several properties distinct from CSD, including sensitivity to AMPA and GABA (Copyright © 2026 The Authors. Published by Elsevier B.V. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare no conflict of interest. |
| Contributed Indexing: | Keywords: Cerebellum; Episodic Ataxia type 1; Kv1.1 channel; Spreading depression |
| Substance Nomenclature: | 147173-20-4 (Kv1.1 Potassium Channel) |
| SCR Disease Name: | Episodic Ataxia, Type 1 |
| Entry Date(s): | Date Created: 20260526 Date Completed: 20260708 Latest Revision: 20260708 |
| Update Code: | 20260708 |
| DOI: | 10.1016/j.bbadis.2026.168302 |
| PMID: | 42191098 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1879-260X |
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| DOI: | 10.1016/j.bbadis.2026.168302 |