Pannexin1 (Panx1) is an ATP release channel expressed in neurons and astrocytes that plays important roles in CNS physiology and pathology. Evidence for the involvement of Panx1 in seizures includes the reduction of epileptiform activity and ictal discharges following Panx1 channel blockade or deletion. However, very little is known about the relative contribution of astrocyte and neuronal Panx1 channels to hyperexcitability. To this end, mice with global and cell type specific deletion of Panx1 were used in one in vivo and two in vitro seizure models. In the low-Mg²⁺ in vitro model, global deletion but not cell-type specific deletion of Panx1 reduced the frequency of epileptiform discharges. This reduced frequency of discharges did not impact the overall power spectra obtained from local field potentials. In the in vitro KA model, in contrast, global or cell type specific deletion of Panx1 did not affect the frequency of discharges, but reduced the overall power spectra. EEG recordings following KA-injection in vivo revealed that although global deletion of Panx1 did not affect the onset of status epilepticus (SE), SE onset was delayed in mice lacking neuronal Panx1 and accelerated in mice lacking astrocyte Panx1. EEG power spectral analysis disclosed a Panx1-dependent cortical region effect; while in the occipital region, overall spectral power was reduced in all three Panx1 genotypes; in the frontal cortex, the overall power was not affected by deletion of Panx1. Together, our results show that the contribution of Panx1 to ictal activity is model, cell-type and brain region dependent.

Pannexin1 (Panx1) 是一种在神经元和星形胶质细胞中表达的 ATP 释放通道，在 CNS 生理学和病理学中起重要作用。Panx1 参与癫痫发作的证据包括 Panx1 通道阻断或缺失后癫痫样活动和发作放电的减少。然而，关于星形胶质细胞和神经元 Panx1 通道对过度兴奋的相对贡献知之甚少。为此，在一个体内和两个体外癫痫模型中使用了具有 Panx1 全局和细胞类型特异性缺失的小鼠。在低 Mg ²⁺ 体外模型中，Panx1 的全局缺失而非细胞类型特异性缺失降低了癫痫样放电的频率。这种降低的放电频率不会影响从局部场电位获得的整体功率谱。在体外KA模型，与此相反，Panx1的全球或细胞类型特异性缺失不影响放电的频率，但降低了整体功率谱。体内KA 注射后的脑电图记录揭示尽管 Panx1 的整体缺失不影响癫痫持续状态 (SE) 的发作，但 SE 发作在缺乏神经元 Panx1 的小鼠中延迟，在缺乏星形胶质细胞 Panx1 的小鼠中加速。EEG 功率谱分析揭示了一种依赖于 Panx1 的皮质区域效应；而在枕骨区，所有三个 Panx1 基因型的整体光谱功率都降低了；在额叶皮层中，整体功率不受 Panx1 删除的影响。总之，我们的结果表明 Panx1 对发作活动的贡献取决于模型、细胞类型和大脑区域。