Astrocyte and Neuronal Pannexin1 Contribute Distinctly to Seizures

ASN Neuro. 2019 Jan-Dec;11:1759091419833502. doi: 10.1177/1759091419833502.


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.

Keywords: astrocytes; epilepsy; ion channels; neuro degeneration; neuro glia; neuro signaling.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenosine Kinase / antagonists & inhibitors
  • Adenosine Kinase / metabolism
  • Adenosine Triphosphate / metabolism
  • Animals
  • Astrocytes / drug effects
  • Astrocytes / metabolism*
  • Brain / drug effects
  • Brain / metabolism
  • Connexins / genetics
  • Connexins / metabolism*
  • Disease Models, Animal
  • Epilepsy / drug therapy
  • Epilepsy / metabolism
  • Kainic Acid
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurons / drug effects
  • Neurons / metabolism*
  • Seizures / drug therapy
  • Seizures / metabolism*


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