KATP channel mutation disrupts hippocampal network activity and nocturnal gamma shifts.

Autor:	Burkart ME; Carl-Ludwig-Institute for Physiology, Faculty of Medicine, Leipzig University, Leipzig 04103, Germany., Kurzke J; Carl-Ludwig-Institute for Physiology, Faculty of Medicine, Leipzig University, Leipzig 04103, Germany., Jacobi R; Department for Neurophysiology, Institute for Physiology, Julius-Maximilians-University Würzburg, Würzburg 97070, Germany., Vera J; Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA., Ashcroft FM; Henry Wellcome Centre for Gene Function, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UK., Eilers J; Carl-Ludwig-Institute for Physiology, Faculty of Medicine, Leipzig University, Leipzig 04103, Germany., Lippmann K; Carl-Ludwig-Institute for Physiology, Faculty of Medicine, Leipzig University, Leipzig 04103, Germany.
Jazyk:	angličtina
Zdroj:	Brain : a journal of neurology [Brain] 2024 Dec 03; Vol. 147 (12), pp. 4200-4212.
DOI:	10.1093/brain/awae157
Abstrakt:	ATP-sensitive potassium (KATP) channels couple cell metabolism to cellular electrical activity. Humans affected by severe activating mutations in KATP channels suffer from developmental delay, epilepsy and neonatal diabetes (DEND syndrome). While the aetiology of diabetes in DEND syndrome is well understood, the pathophysiology of the neurological symptoms remains unclear. We hypothesized that impaired activity of parvalbumin-positive interneurons (PV-INs) may result in seizures and cognitive problems. We found, by performing electrophysiological experiments, that expressing the DEND mutation Kir6.2-V59M selectively in mouse PV-INs reduced intrinsic gamma frequency preference and short-term depression as well as disturbed cognition-associated gamma oscillations and hippocampal sharp waves. Furthermore, the risk of seizures was increased and the day-night shift in gamma activity disrupted. Blocking KATP channels with tolbutamide partially rescued the network oscillations. The non-reversible part may, to some extent, result from observed altered PV-IN dendritic branching and PV-IN arrangement within CA1. In summary, PV-INs play a key role in DEND syndrome, and this provides a framework for establishing treatment options. (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Databáze:	MEDLINE
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