Methods: We used electroencephalographic recordings in freely moving Genetic
Absence Epilepsy Rats From Strasbourg (GAERSs) to assess the action of oral administration of ivabradine, with and without elacridar, on ASs. Ivabradine was also microinjected into the CIN and VB of GAERSs in vivo and applied to Wistar CIN and GAERS VB slices while recording patch-clamped cortical Layer 5/6 and thalamocortical neurons, respectively.
Results: Oral administration of ivabradine markedly and dose-dependently reduced ASs. Ivabradine injection into CIN abolished ASs and elicited small-amplitude 4–7-Hz waves (without spikes), whereas in the VB it was less potent. Moreover, ivabradine applied to GAERS VB and Wistar CIN slices selectively decreased HCN channel-dependent properties of cortical Layer 5/6 pyramidal and thalamocortical neurons, respectively.
Significance: These results provide the first demonstration of the antiabsence action of a systemically administered HCN channel blocker, indicating the potential of this class of drugs as a novel therapeutic avenue for ASs.
Bibliographical note© 2021 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Funding: Wellcome Trust, Grant/Award Number: 91882; Országos Tudományos Kutatási Alapprogramok, Grant/Award Number: FK123831 and NN125601; Hungarian Brain Research Program, Grant/Award Number: KTIA_NAP_13-2-2014-0014; Ministry of Human Capacities, Hungary, Grant/Award Number: 20391-3/2018/FEKUSTRAT; Marie Skłodowska-Curie Actions, Grant/Award Number: H2020-MSCA-ITN-2016-722053; Ester Floridia Neuroscience Research Foundation; Magor L. Lőrincz is a grantte of the János Bolyai Fellowship.
- Childhood absence epilepsy
- lh current
- thalamocortical neurons