Biological Faculty, Saint Petersburg State University, 199034 St. Petersburg, Russia.
Institute of Translational Biomedicine, Saint Petersburg State University, 199034 St. Petersburg, Russia.
Int J Mol Sci. 2022 Jan 8;23(2):663. doi: 10.3390/ijms23020663.
Gap junctions (GJs) are intercellular junctions that allow the direct transfer of ions and small molecules between neighboring cells, and GJs between astrocytes play an important role in the development of various pathologies of the brain, including regulation of the pathological neuronal synchronization underlying epileptic seizures. Recently, we found that a pathological change is observed in astrocytes during the ictal and interictal phases of 4-aminopyridin (4-AP)-elicited epileptic activity in vitro, which was correlated with neuronal synchronization and extracellular epileptic electrical activity. This finding raises the question: Does this signal depend on GJs between astrocytes? In this study we investigated the effect of the GJ blocker, carbenoxolone (CBX), on epileptic activity in vitro and in vivo. Based on the results obtained, we came to the conclusion that the astrocytic syncytium formed by GJ-associated astrocytes, which is responsible for the regulation of potassium, affects the formation of epileptic activity in astrocytes in vitro and epileptic seizure onset. This effect is probably an important, but not the only, mechanism by which CBX suppresses epileptic activity. It is likely that the mechanisms of selective inhibition of GJs between astrocytes will show important translational benefits in anti-epileptic therapies.
缝隙连接（GJ）是细胞间的连接，允许离子和小分子在相邻细胞之间直接转移，而星形胶质细胞之间的 GJ 在大脑的各种病理发展中起着重要作用，包括调节癫痫发作下病理性神经元同步。最近，我们发现，在体外的 4-氨基吡啶（4-AP）诱发的癫痫活动的发作期和发作间期，星形胶质细胞中观察到一种病理性变化，这与神经元同步和细胞外癫痫电活动有关。这一发现提出了一个问题：这种信号是否依赖于星形胶质细胞之间的 GJ？在这项研究中，我们研究了缝隙连接阻滞剂 carbenoxolone（CBX）对体外和体内癫痫活动的影响。基于获得的结果，我们得出结论，由 GJ 相关星形胶质细胞形成的星形胶质细胞合胞体负责调节钾，影响体外星形胶质细胞中癫痫活动的形成和癫痫发作的开始。这种影响可能是 CBX 抑制癫痫活动的一个重要但不是唯一的机制。星形胶质细胞之间的 GJ 的选择性抑制机制可能在抗癫痫治疗中显示出重要的转化益处。
