最近发现星型胶质细胞能释放谷氨酸、ATP、丝氨酸等胶质递质，与神经元相互调控，参与癫痫发病。申请人前期工作发现可调控ATPase活性的钙/钙调蛋白结合蛋白calponin-3不仅在癫痫患者及动物神经元和星型胶质细胞过表达，沉默/过表达其CNN3基因还会改变鼠的癫痫易感性。但尚未见研究星形胶质细胞calponin-3表达改变意义和机制的报道。故我们提出假说：异常的calponin-3可改变脑细胞中ATPase及CaMKⅡ的活性，破坏星形胶质细胞-神经元网络稳态，进而促成癫痫发作。为此，我们将通过患者脑组织、实验鼠，利用免疫染色、western blot、定磷法、放射酶法、条件性基因敲除和行为学观察等手段，明确星形胶质细胞calponin-3蛋白过表达参与癫痫发作的调控机制。本研究将从calponin-3这个新视点揭示星形胶质细胞-神经元网络调控机制和为开发新型抗癫痫药奠定基础。

Recent studies suggest that astrocytes release gliotransmitters (e.g. glutamate, D-serine and ATP), interact with neurons, and contribute to seizures. Calponin-3 is a calcium and calmodulin binding protein, and may inhibit the activity of ATPase. Our previous studies show that the level of neuronal and astrocyte calponin-3 in epileptic patients and animals were significantly up-regulated. Additionally, the susceptibility to epilepsy in experimental rats was changed after silencing or over-expression of CNN3 gene. However, we failed to find any article related to abnormal calponin-3 in the astrocytes. Thus we hypothese that abnormal calponin-3 may influence the activity of cellar ATPase and CaMKⅡin the brain, interrupt homeostasis astrocyte-neuron network, and contribute to epilepsy. We plan to study seizure modulation by calponin-3 in astrocytes on the brain tissue of epileptic patient and animal model, using immunohistochemistry and western blot and conditional knockout of CNN3 gene and observation etc. The study may help to reveal how to modulate astrocyte-neuron network, and lay a foundation for development of new antiepileptic drugs.