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Alterations in the Distribution of GABAA Receptors in Epilepsy.

Authors

Houser CR1,2, Zhang N1, Peng Z1.

Source

Jasper's Basic Mechanisms of the Epilepsies [Internet]. 4th edition. Bethesda (MD): National Center for Biotechnology Information (US); 2012.

Author information

1
Department of Neurobiology, David Geffen School of Medicine at UCLA, CA 90095
2
VA Greater Los Angeles Healthcare System, West Los Angeles, Los Angeles, CA 90073

Excerpt

Multiple changes in the localization of GABAA receptor (GABAAR) subunits have been identified in human temporal lobe epilepsy and related animal models of acquired epilepsy. Despite the complexities associated with increased and decreased expression of different subunits, several interesting patterns are emerging. First, subunits that mediate tonic inhibition, such as δ and α5, show the most consistent decreases in several epilepsy models and appear more likely to be decreased than many subunits that mediate phasic inhibition. Unexpectedly, tonic inhibition often appears to be preserved, suggesting that more complex changes are occurring, including changes in the subunit composition of remaining receptors. However, the remaining receptors show decreased responses to certain modulators, such as neurosteroids, that normally increase the responsiveness of GABAARs at times of stress and hormonal fluctuations. Studies also suggest that even increased expression of some GABAAR subunits, such as α4, could lead to compromised inhibition by changing the kinetic properties and pharmacology of the receptors. Such changes could be particularly detrimental at times when increased inhibitory responses are needed to control network activity. The multiple types of changes emphasize the remarkable plasticity of GABAARs and challenge investigators to utilize this plasticity in the development of new approaches to the treatment of epilepsy.

Copyright © 2012, Michael A Rogawski, Antonio V Delgado-Escueta, Jeffrey L Noebels, Massimo Avoli and Richard W Olsen.

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