ATP- and adenosine-mediated signaling are prominent types of glia-glia and glia-neuron interaction, with an imbalance of ATP/adenosine ratio leading to altered states of excitability, as seen in epileptic seizures. Pannexin1 (Panx1), a member of the gap junction family, is an ATP release channel that is expressed in astrocytes and neurons. Previous studies provided evidence supporting a role for purinergic-mediated signaling via Panx1 channels in seizures; using mice with global deletion of Panx1, it was shown that these channels contribute in maintenance of seizures by releasing ATP. However, nothing is known about the extent to which astrocyte and neuronal Panx1 might differently contribute to seizures. We here show that targeted deletion of Panx1 in astrocytes or neurons has opposing effects on acute seizures induced by kainic acid. The absence of Panx1 in astrocytes potentiates while the absence of Panx1 in neurons attenuates seizure manifestation. Immunohistochemical analysis performed in brains of these mice, revealed that adenosine kinase (ADK), an enzyme that regulates extracellular levels of adenosine, was increased only in seized GFAP-Cre:Panx1f/f mice. Pretreating mice with the ADK inhibitor, idotubercidin, improved seizure outcome and prevented the increase in ADK immunoreactivity. Together, these data suggest that the worsening of seizures seen in mice lacking astrocyte Panx1 is likely related to low levels of extracellular adenosine due to the increased ADK levels in astrocytes. Our study not only reveals an unexpected link between Panx1 channels and ADK but also highlights the important role played by astrocyte Panx1 channels in controlling neuronal activity.

中文翻译：

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星形胶质细胞和神经元Pannexin1明显有助于癫痫发作。

ATP和腺苷介导的信号传导是神经胶质-神经胶质细胞和神经胶质-神经元相互作用的主要类型，ATP /腺苷比例的失衡导致兴奋性状态改变，如癫痫发作中所见。缝隙连接家族的成员Pannexin1（Panx1）是在星形胶质细胞和神经元中表达的ATP释放通道。先前的研究提供了证据，证明癫痫发作中通过Panx1通道在嘌呤能介导的信号传导中发挥作用。使用Panx1整体缺失的小鼠，表明这些通道通过释放ATP有助于维持癫痫发作。但是，关于星形胶质细胞和神经元Panx1可能在何种程度上促成癫痫发作，尚无定论。我们在这里显示，星形胶质细胞或神经元中Panx1的靶向缺失对海藻酸诱导的急性癫痫发作有相反的影响。星形胶质细胞中Panx1的缺乏增强，而神经元中Panx1的缺乏减弱癫痫发作的表现。在这些小鼠的大脑中进行的免疫组织化学分析表明，腺苷激酶（ADK）是一种调节细胞外腺苷水平的酶，仅在被检出的GFAP-Cre：Panx1f / f小鼠中增加。用ADK抑制剂idotubercidin预处理小鼠可改善癫痫发作的预后并防止ADK免疫反应性增加。总之，这些数据表明，在缺乏星形胶质细胞Panx1的小鼠中癫痫发作的恶化可能与星形胶质细胞中ADK含量升高引起的细胞外腺苷水平低有关。我们的研究不仅揭示了Panx1通道与ADK之间的意外联系，还强调了星形胶质细胞Panx1通道在控制神经元活动中的重要作用。