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The Paroxysmal Depolarization Shift: Reconsidering Its Role in Epilepsy, Epileptogenesis and Beyond

Center of Physiology and Pharmacology, Department of Neurophysiology and Neuropharmacology, Medical University of Vienna, Waehringerstrasse 13a, 1090 Vienna, Austria
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Int. J. Mol. Sci. 2019, 20(3), 577; https://doi.org/10.3390/ijms20030577
Received: 8 January 2019 / Accepted: 24 January 2019 / Published: 29 January 2019
(This article belongs to the Special Issue Epilepsy: From Molecular Mechanisms to Targeted Therapies)
Paroxysmal depolarization shifts (PDS) have been described by epileptologists for the first time several decades ago, but controversy still exists to date regarding their role in epilepsy. In addition to the initial view of a lack of such a role, seemingly opposing hypotheses on epileptogenic and anti-ictogenic effects of PDS have emerged. Hence, PDS may provide novel targets for epilepsy therapy. Evidence for the roles of PDS has often been obtained from investigations of the multi-unit correlate of PDS, an electrographic spike termed “interictal” because of its occurrence during seizure-free periods of epilepsy patients. Meanwhile, interictal spikes have been found to be associated with neuronal diseases other than epilepsy, e.g., Alzheimer’s disease, which may indicate a broader implication of PDS in neuropathologies. In this article, we give an introduction to PDS and review evidence that links PDS to pro- as well as anti-epileptic mechanisms, and to other types of neuronal dysfunction. The perturbation of neuronal membrane voltage and of intracellular Ca2+ that comes with PDS offers many conceivable pathomechanisms of neuronal dysfunction. Out of these, the operation of L-type voltage-gated calcium channels, which play a major role in coupling excitation to long-lasting neuronal changes, is addressed in detail. View Full-Text
Keywords: hippocampal neurons; L-type voltage-gated calcium channels; seizures; Alzheimer’s disease; electrophysiology; neuronal dysfunction; giant depolarizing potentials; neuronal remodelling; dendrites hippocampal neurons; L-type voltage-gated calcium channels; seizures; Alzheimer’s disease; electrophysiology; neuronal dysfunction; giant depolarizing potentials; neuronal remodelling; dendrites
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MDPI and ACS Style

Kubista, H.; Boehm, S.; Hotka, M. The Paroxysmal Depolarization Shift: Reconsidering Its Role in Epilepsy, Epileptogenesis and Beyond. Int. J. Mol. Sci. 2019, 20, 577. https://doi.org/10.3390/ijms20030577

AMA Style

Kubista H, Boehm S, Hotka M. The Paroxysmal Depolarization Shift: Reconsidering Its Role in Epilepsy, Epileptogenesis and Beyond. International Journal of Molecular Sciences. 2019; 20(3):577. https://doi.org/10.3390/ijms20030577

Chicago/Turabian Style

Kubista, Helmut; Boehm, Stefan; Hotka, Matej. 2019. "The Paroxysmal Depolarization Shift: Reconsidering Its Role in Epilepsy, Epileptogenesis and Beyond" Int. J. Mol. Sci. 20, no. 3: 577. https://doi.org/10.3390/ijms20030577

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