Aquilino Mark S, Whyte-Fagundes Paige, Zoidl Georg, Carlen Peter L
IBBME, University of Toronto, Rosebrugh Building, Room 407, 164 College St, Toronto, ON, M5S 3G9, Canada; Krembil Research Institute, University Health Network, 135 Nassau St, Toronto, ON, M5T 1M8, Canada.
York University, 4700 Keele St, Toronto, ON, M3J 1P3, Canada.
Neurosci Lett. 2019 Mar 16;695:71-75. doi: 10.1016/j.neulet.2017.09.004. Epub 2017 Sep 5.
Pannexin-1 (Panx1) expression is raised in several animal seizure models and in resected human epileptic brain tissue, suggesting relevance to epilepsy. Multiple factors that are characteristic of seizures are thought to regulate Panx1 channel opening, including elevated levels of extracellular K. Panx1, when open, 1) releases ATP, glutamate, and other metabolites into the extracellular medium, and 2) may depolarize the membrane due to a channel reversal potential around 0mV. Resultant ATP release from stimulated Panx1 can activate purinergic receptors, including P2X7 receptors. Glutamate and other signaling molecules released by Panx1 opening may have both excitatory and inhibitory actions on seizure generation. This review examines the critical and complex roles of Panx1 channels in epilepsy, which could provide a basis for future therapeutics.
泛连接蛋白-1（Panx1）在多种动物癫痫模型以及切除的人类癫痫脑组织中表达上调，提示其与癫痫有关。多种具有癫痫特征的因素被认为可调节Panx1通道开放，包括细胞外钾离子水平升高。Panx1开放时，1）会将三磷酸腺苷（ATP）、谷氨酸及其他代谢产物释放到细胞外介质中，2）由于通道反转电位约为0mV，可能使细胞膜去极化。受刺激的Panx1释放的ATP可激活嘌呤能受体，包括P2X7受体。Panx1开放释放的谷氨酸及其他信号分子可能对癫痫发作具有兴奋和抑制双重作用。本综述探讨了Panx1通道在癫痫中至关重要且复杂的作用，这可为未来的治疗提供依据。
