The report was presented at the Epilepsy Research UK International Expert Workshop Why do some brains seize? Molecular, cellular and network mechanisms, which took place in Oxford, UK on 15–16 March 2012.
Cortical inhibition, pH and cell excitability in epilepsy: what are optimal targets for antiepileptic interventions?
Article first published online: 21 NOV 2012
© 2012 The Authors. The Journal of Physiology © 2012 The Physiological Society
The Journal of Physiology
Volume 591, Issue 4, pages 765–774, February 2013
How to Cite
Pavlov, I., Kaila, K., Kullmann, D. M. and Miles, R. (2013), Cortical inhibition, pH and cell excitability in epilepsy: what are optimal targets for antiepileptic interventions?. The Journal of Physiology, 591: 765–774. doi: 10.1113/jphysiol.2012.237958
- Issue published online: 14 FEB 2013
- Article first published online: 21 NOV 2012
- Accepted manuscript online: 22 AUG 2012 12:00AM EST
- (Received 1 June 2012; accepted after revision 10 August 2012; first published online 13 August 2012)
Abstract Epilepsy is characterised by the propensity of the brain to generate spontaneous recurrent bursts of excessive neuronal activity, seizures. GABA-mediated inhibition is critical for restraining neuronal excitation in the brain, and therefore potentiation of GABAergic neurotransmission is commonly used to prevent seizures. However, data obtained in animal models of epilepsy and from human epileptic tissue suggest that GABA-mediated signalling contributes to interictal and ictal activity. Prolonged activation of GABAA receptors during epileptiform bursts may even initiate a shift in GABAergic neurotransmission from inhibitory to excitatory and so have a proconvulsant action. Direct targeting of the membrane mechanisms that reduce spiking in glutamatergic neurons may better control neuronal excitability in epileptic tissue. Manipulation of brain pH may be a promising approach and recent advances in gene therapy and optogenetics seem likely to provide further routes to effective therapeutic intervention.