title: Targeting pannexin1 improves seizure outcome.
abstract: Imbalance of the excitatory neurotransmitter glutamate and of the inhibitory neurotransmitter GABA is one of several causes of seizures. ATP has also been implicated in epilepsy. However, little is known about the mechanisms involved in the release of ATP from cells and the consequences of the altered ATP signaling during seizures. Pannexin1 (Panx1) is found in astrocytes and in neurons at high levels in the embryonic and young postnatal brain, declining in adulthood. Panx1 forms large-conductance voltage sensitive plasma membrane channels permeable to ATP that are also activated by elevated extracellular K(+) and following P2 receptor stimulation. Based on these properties, we hypothesized that Panx1 channels may contribute to seizures by increasing the levels of extracellular ATP. Using pharmacological tools and two transgenic mice deficient for Panx1 we show here that interference with Panx1 ameliorates the outcome and shortens the duration of kainic acid-induced status epilepticus. These data thus indicate that the activation of Panx1 in juvenile mouse hippocampi contributes to neuronal hyperactivity in seizures.
authors.affiliation: The Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, New York, New York, United States of America.
authors.forename: Marcelo F
authors.initials: MF
authors.lastname: Santiago
authors.forename: Jana
authors.initials: J
authors.lastname: Veliskova
authors.forename: Naman K
authors.initials: NK
authors.lastname: Patel
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Lutz
authors.forename: Dorothee
authors.initials: D
authors.lastname: Caille
authors.forename: Anne
authors.initials: A
authors.lastname: Charollais
authors.forename: Paolo
authors.initials: P
authors.lastname: Meda
authors.forename: Eliana
authors.initials: E
authors.lastname: Scemes
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects*; D015153:Blotting, Western; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D017630:Connexins / Q000502:physiology*; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D007608:Kainic Acid / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D013226:Status Epilepticus / Q000378:metabolism
chemical_list: D017630:Connexins; D009419:Nerve Tissue Proteins; C503631:Panx1 protein, mouse; D000255:Adenosine Triphosphate; D011188:Potassium; D007608:Kainic Acid