Pannexin-1 channels contribute to seizure generation in human epileptic brain tissue and in a mouse model of epilepsy

Science Translational Medicine
Elena DossiNathalie Rouach

Abstract

Epilepsies are characterized by recurrent seizures, which disrupt normal brain function. Alterations in neuronal excitability and excitation-inhibition balance have been shown to promote seizure generation, yet molecular determinants of such alterations remain to be identified. Pannexin channels are nonselective, large-pore channels mediating extracellular exchange of neuroactive molecules. Recent data suggest that these channels are activated under pathological conditions and regulate neuronal excitability. However, whether pannexin channels sustain or counteract chronic epilepsy in human patients remains unknown. We studied the impact of pannexin-1 channel activation in postoperative human tissue samples from patients with epilepsy displaying epileptic activity ex vivo. These samples were obtained from surgical resection of epileptogenic zones in patients suffering from lesional or drug-resistant epilepsy. We found that pannexin-1 channel activation promoted seizure generation and maintenance through adenosine triphosphate signaling via purinergic 2 receptors. Pharmacological inhibition of pannexin-1 channels with probenecid or mefloquine-two medications currently used for treating gout and malaria, respectively-blocked ictal...Continue Reading

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