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ATP- and adenosine-mediated signaling are prominent types of glia-glia and glia-neuron interaction, with an imbalance of ATP/adenosine ratio leading to altered states of excitability, as seen in epileptic seizures. Pannexin1 (Panx1), a member of the gap junction family, is an ATP release channel that is expressed in astrocytes and neurons. Previous studies provided evidence supporting a role for purinergic-mediated signaling via Panx1 channels in seizures; using mice with global deletion of Panx1, it was shown that these channels contribute in maintenance of seizures by releasing ATP. However, nothing is known about the extent to which astrocyte and neuronal Panx1 might differently contribute to seizures. We here show that targeted deletion of Panx1 in astrocytes or neurons has opposing effects on acute seizures induced by kainic acid. The absence of Panx1 in astrocytes potentiates while the absence of Panx1 in neurons attenuates seizure manifestation. Immunohistochemical analysis performed in brains of these mice, revealed that adenosine kinase (ADK), an enzyme that regulates extracellular levels of adenosine, was increased only in seized GFAP-Cre:Panx1f/f mice. Pretreating mice with the ADK inhibitor, idotubercidin, improved seizure outcome and prevented the increase in ADK immunoreactivity. Together, these data suggest that the worsening of seizures seen in mice lacking astrocyte Panx1 is likely related to low levels of extracellular adenosine due to the increased ADK levels in astrocytes. Our study not only reveals an unexpected link between Panx1 channels and ADK but also highlights the important role played by astrocyte Panx1 channels in controlling neuronal activity.
Pubmed ID: 30862176 RIS Download
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Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsAn Antibody supplier and subset of ThermoFisher Scientific which provides fluorescence reagents for various experiments and methods.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsThis polyclonal targets GFAP N-Terminal antibody produced in rabbit
View all literature mentionsThis unknown targets Rabbit IgG (H+L)
View all literature mentionsThis unknown targets Rabbit IgG (H+L)
View all literature mentionsThis polyclonal targets Mouse IgG
View all literature mentionsThis monoclonal targets Mouse Human GAPDH Clone 6C5
View all literature mentionsThis polyclonal targets goat anti-rabbit IgG-HRP
View all literature mentionsMus musculus with name STOCK Gt(ROSA)26Sortm1.1(CAG-EGFP)Fsh/Mmjax from MMRRC.
View all literature mentionsgene symbol note: pannexin 1 mutant strain This is a legacy resource.
View all literature mentionsThis polyclonal targets GFAP N-Terminal antibody produced in rabbit
View all literature mentionsThis unknown targets Rabbit IgG (H+L)
View all literature mentionsThis unknown targets Rabbit IgG (H+L)
View all literature mentionsThis polyclonal targets Mouse IgG
View all literature mentionsThis monoclonal targets Mouse Human GAPDH Clone 6C5
View all literature mentionsThis polyclonal targets GFAP N-Terminal antibody produced in rabbit
View all literature mentionsgene symbol note: pannexin 1 mutant strain This is a legacy resource.
View all literature mentionsAllele Detail: Transgenic This is a legacy resource.
View all literature mentionsAllele Detail: Targeted, Transgenic This is a legacy resource.
View all literature mentionsThis monoclonal targets Mouse Human GAPDH Clone 6C5
View all literature mentionsThis unknown targets Rabbit IgG (H+L)
View all literature mentionsThis polyclonal targets GFAP N-Terminal antibody produced in rabbit
View all literature mentionsAllele Detail: Transgenic This is a legacy resource.
View all literature mentionsAllele Detail: Targeted, Transgenic This is a legacy resource.
View all literature mentionsgene symbol note: pannexin 1 mutant strain This is a legacy resource.
View all literature mentionsThis unknown targets Rabbit IgG (H+L)
View all literature mentionsThis polyclonal targets goat anti-rabbit IgG-HRP
View all literature mentionsThis polyclonal targets Mouse IgG
View all literature mentionsThis polyclonal targets GFAP N-Terminal antibody produced in rabbit
View all literature mentionsThis polyclonal targets goat anti-rabbit IgG-HRP
View all literature mentionsgene symbol note: pannexin 1 mutant strain This is a legacy resource.
View all literature mentionsAllele Detail: Transgenic This is a legacy resource.
View all literature mentionsMus musculus with name STOCK Gt(ROSA)26Sortm1.1(CAG-EGFP)Fsh/Mmjax from MMRRC.
View all literature mentionsThis unknown targets Rabbit IgG (H+L)
View all literature mentionsThis polyclonal targets Mouse IgG
View all literature mentionsThis unknown targets Rabbit IgG (H+L)
View all literature mentionsThis polyclonal targets GFAP N-Terminal antibody produced in rabbit
View all literature mentionsThis monoclonal targets Mouse Human GAPDH Clone 6C5
View all literature mentionsAllele Detail: Targeted, Transgenic This is a legacy resource.
View all literature mentionsAllele Detail: Transgenic This is a legacy resource.
View all literature mentionsAllele Detail: Targeted, Transgenic This is a legacy resource.
View all literature mentionsThis polyclonal targets GFAP N-Terminal antibody produced in rabbit
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