Department of Cell Biology & Anatomy, New York Medical College, Valhalla, New York, United States.
Department of Neurology, New York Medical College, Valhalla, New York, United States.
ASN Neuro. 2021 Jan-Dec;13:17590914211007273. doi: 10.1177/17590914211007273.
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 and two seizure models. In the low-Mg 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 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 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.
连接蛋白 1（Panx1）是一种在神经元和星形胶质细胞中表达的 ATP 释放通道，在中枢神经系统生理和病理中发挥重要作用。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，对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，使用具有 Panx1 全局和细胞类型特异性缺失的小鼠进行了一项 和两项 癫痫发作模型研究。在低镁模型中，Panx1 的全局缺失而不是细胞类型特异性缺失减少了癫痫样放电的频率。这种放电频率的降低并不影响从局部场电位获得的总体功率谱。相比之下，在 KA 模型中，Panx1 的全局或细胞类型特异性缺失均不影响放电频率，但降低了总体功率谱。KA 注射后的 EEG 记录显示，尽管 Panx1 的全局缺失不影响癫痫持续状态（SE）的发作，但神经元 Panx1 缺失的小鼠 SE 发作延迟，而星形胶质细胞 Panx1 缺失的小鼠 SE 发作加速。EEG 功率谱分析揭示了 Panx1 依赖性皮质区域效应；在枕叶区域，所有三种 Panx1 基因型的总谱功率均降低；在额叶皮层，Panx1 缺失不影响总谱功率。总之，我们的结果表明，Panx1 对发作活动的贡献取决于模型、细胞类型和脑区。
