IJPPP Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Int J Physiol Pathophysiol Pharmacol 2012;4(4):174-187

Review Article
P2X7 receptor in epilepsy; role in pathophysiology and
potential targeting for seizure control

Tobias Engel, Alba Jimenez-Pacheco, Maria Teresa Miras-Portugal, Miguel Diaz-Hernandez, David C Henshall

Department of Physiology & Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland; Centre for
the Study of Neurological Disorders, Royal College of Surgeons in Ireland, Dublin, Ireland; Instituto de Neuroquimica
de la UCM, Universidad Complutense de Madrid, Madrid, Spain; Instituto de Investigación Sanitaria del
Hospital Clinico San Carlos (IdISSC), Madrid, Spain

Received December 17, 2012; Accepted December 25, 2012; Epub December 26, 2012; Published December
31, 2012

Abstract: The P2X7 receptor is an ATP-gated non-selective cation-permeable ionotropic receptor selectively expressed
in neurons and glia in the brain. Activation of the P2X7 receptor has been found to modulate neuronal excitability
in the hippocampus and it has also been linked to microglia activation and neuroinflammatory responses.
Accordingly, interest developed on the P2X7 receptor in disorders of the nervous system, including epilepsy. Studies
show that expression of the P2X7 receptor is elevated in damaged regions of the brain after prolonged seizures
(status epilepticus) in both neurons and glia. P2X7 receptor expression is also increased in the hippocampus in
experimental epilepsy. Recent data show that mice lacking the P2X7 receptor display altered susceptibility to status
epilepticus and that drugs targeting the P2X7 receptor have potent anticonvulsant effects. Together, this suggests
that P2X7 receptor ligands may be useful adjunctive treatments for refractory status epilepticus or perhaps pharmacoresistant
epilepsy. This review summarizes the evidence of P2X7 receptor involvement in the pathophysiology
of epilepsy and the potential of drugs targeting this receptor for seizure control. (IJPPP1212005).

Keywords: Adenosine 5’-triphosphate, anticonvulsant, epilepsy, hippocampal sclerosis, interleukin 1 beta, status

Address all correspondence to:
Dr. David C Henshall
Department of Physiology and Medical Physics
Royal College of Surgeons in Ireland
123 St. Stephen’s Green, Dublin 2, Ireland.
Phone:+35314028629; Fax: +35314022447
E-mail: dhenshall@rcsi.ie