Activation of A1 receptor suppresses glutamate release from pre-synaptic terminals and hyperpolarizes post synaptic neurons via ATP-sensitive potassium channels. During seizures, extracellular adenosine levels rise substantially, due to the hydrolysis of ATP by ectonucleotidases, and to the release of adenosine through the equilibrative nucleoside transporters as a consequence of down-regulation/inhibiton of adenosine kinase. However, under conditions mimicking status epilepticus, it was shown that the loss of adenosine-mediated inhibition was correlated with the depletion of cellular ATP that occurred during the spontaneous switch between seizure-like events to late recurrent discharges. It was also reported that such a cellular depletion of ATP results in the reduction of the phosphorylation state and function of the GABA-A receptors leading to increased number of after-discharges. Thus, based on these reports, we can speculate that the beneficial effect seen here in the Panx1-null mice could be resultant from the prevention of total loss of cellular ATP that impairs animal recovery from prolonged seizures. Alternatively or in addition, it is also possible that the reduced release of ATP from Panx1-null mice could also limit the activation of excitatory P2X receptors and thus the progression of status epilepticus. In summary, our results provide the first direct evidence that Panx1 channels worsen OTX015 seizures and sustain status epilepticus in vivo. While further studies are now required to differentiate the respective contributions of the neuronal and glial Panx1 and to conclusively determine the contribution of ATP/P2X receptors to this deleterious condition, the data open new perspectives for the development of innovative therapeutic approaches which, by targeting the Panx1, may be beneficial for the prevention and/or treatment of status epilepticus. Neural plakophilin-related armadillo protein is a neuronal-specific protein that was first reported in a sequence search for plakophilin 1 homologous proteins. Shortly after, clones encoding the human NPRAP were isolated from brain cDNA libraries as a presenilin-1 biochemical partner, the then discovered and most commonly mutated protein in familial Alzheimer’s disease. CDCS features include a high-pitched cry at birth due to abnormal larynx development, low-set ears, microencephaly and severe psychomotor and mental retardation. Symptom severity and the deletion size in the 5p chromosome vary, and, although another synaptic gene is located within the critical region, refined genotypic/phenotypic studies have revealed that the hemizygous loss of CTNND2, in particular, correlates with the severe mental retardation trait in CDCS patients. Although NPRAP localizes to synapses, and studies in mouse primary neurons have suggested its involvement in a pathway regulating dendritic protrusion elaboration, many armadillo-like proteins and all of the p120-catenin family members have emerging roles in intracellular events. Similarly, NPRAP has strong perikarya localization, along with a weak nuclear signal. It has also been shown to regulate the rapsyn promoter at the neuromuscular junction through its binding to Kaiso.