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: Marcelo F Santiago, Jana Veliskova, Naman K Patel, Sarah E Lutz, Dorothee Caille, Anne Charollais, Paolo Meda, Eliana Scemes
• Journal: PloS one (PLoS One) Vol. 6 Issue 9 Pg. e25178 ( 2011) ISSN: 1932-6203 [Electronic] United States
• PMID: 21949881 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Connexins
• Nerve Tissue Proteins
• Panx1 protein, mouse
• Adenosine Triphosphate
• Potassium
• Kainic Acid

Topics

• Adenosine Triphosphate (metabolism)
• Animals
• Astrocytes (cytology, metabolism)
• Behavior, Animal (drug effects)
• Blotting, Western
• Brain (cytology, metabolism)
• Cells, Cultured
• Connexins (physiology)
• Epilepsy (chemically induced, metabolism, prevention & control)
• Fluorescent Antibody Technique
• Hippocampus (cytology, metabolism)
• Kainic Acid (pharmacology)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Nerve Tissue Proteins (physiology)
• Neurons (cytology, metabolism)
• Potassium (metabolism)
• Seizures (chemically induced, metabolism, prevention & control)
• Status Epilepticus (metabolism)