Targeting pannexin1 improves seizure outcome
| Autor: | Anne Charollais, Dorothée Caille, Naman K. Patel, Paolo Meda, Eliana Scemes, Marcelo F. Santiago, Sarah E. Lutz, Jana Velíšková |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Central Nervous System
Anatomy and Physiology Adenosine Triphosphate/metabolism lcsh:Medicine Fluorescent Antibody Technique Stimulation Pharmacology Status Epilepticus/metabolism Hippocampus Ion Channels Connexins chemistry.chemical_compound Epilepsy Mice 0302 clinical medicine Adenosine Triphosphate Status Epilepticus Hippocampus/cytology/metabolism Brain/cytology/metabolism Causes of seizures Behavior Animal/drug effects lcsh:Science Cells Cultured Neurons 0303 health sciences Multidisciplinary Kainic Acid Behavior Animal Glutamate receptor Brain Neurochemistry Neurotransmitters Nerve Tissue Proteins/physiology Kainic Acid/pharmacology medicine.symptom Neurochemicals Research Article Genetically modified mouse Kainic acid Blotting Western Potassium/metabolism Connexins/physiology Nerve Tissue Proteins Mice Transgenic Status epilepticus Biology Neurological System 03 medical and health sciences Seizures Extracellular medicine Animals ddc:612 030304 developmental biology Astrocytes/cytology/metabolism Epilepsy/chemically induced/metabolism/prevention & control lcsh:R Seizures/chemically induced/metabolism/prevention & control medicine.disease Mice Inbred C57BL chemistry nervous system Cellular Neuroscience Astrocytes Potassium lcsh:Q 030217 neurology & neurosurgery Neurons/cytology/metabolism Neuroscience |
| Zdroj: | PLOS ONE, Vol. 6, No 9 (2011) P. e25178 PLoS ONE PLoS ONE, Vol 6, Iss 9, p e25178 (2011) PloS one PLoS ONE; Vol 6 |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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