Zhao Shidi, Chen Na, Yang Zhilai, Huang Li, Zhu Yan, Guan Sudong, Chen Qianfen, Wang Jin-Hui
Department of Physiology, Bengbu Medical College, Bengbu Anhui 233000, China.
Biochem Biophys Res Commun. 2008 Feb 8;366(2):401-7. doi: 10.1016/j.bbrc.2007.11.173. Epub 2007 Dec 10.
Ischemia-induced excitotoxicity at cerebellar Purkinje cells is presumably due to a persistent glutamate action. To the fact that they are more vulnerable to ischemia than other glutamate-innervated neurons, we studied whether additional mechanisms are present and whether cytoplasm Ca(2+) plays a key role in their ischemic excitotoxicity. Ischemic changes in the excitability of Purkinje cells were measured by whole-cell recording in cerebellar slices of rats with less glutamate action. The role of cytoplasm Ca(2+) was examined by two-photon cellular imaging and BAPTA infusion in Purkinje cells. Lowering perfusion rate to cerebellar slices deteriorated spike timing and raised spike capacity of Purkinje cells. These changes were associated with the reduction of spike refractory periods and threshold potentials, as well as the loss of their control to spike encoding. Ischemia-induced functional deterioration at Purkinje neurons was accompanied by cytoplasm Ca(2+) rise and prevented by BAPTA infusion. Therefore, the ischemia destabilizes the spike encoding of Purkinje cells via raising cytoplasm Ca(2+) without a need for glutamate, which subsequently causes their excitotoxic death.
小脑浦肯野细胞缺血诱导的兴奋性毒性可能归因于谷氨酸的持续作用。鉴于它们比其他谷氨酸支配的神经元更容易受到缺血影响，我们研究了是否存在其他机制，以及细胞质Ca(2+)在其缺血性兴奋性毒性中是否起关键作用。在谷氨酸作用较弱的大鼠小脑切片中，通过全细胞记录来测量浦肯野细胞兴奋性的缺血变化。通过双光子细胞成像和向浦肯野细胞中注入BAPTA来研究细胞质Ca(2+)的作用。降低小脑切片的灌注速率会使浦肯野细胞的动作电位发放时间变差，并提高其发放能力。这些变化与动作电位不应期和阈电位的降低以及对动作电位编码控制的丧失有关。缺血诱导的浦肯野神经元功能恶化伴随着细胞质Ca(2+)升高，并可通过注入BAPTA来预防。因此，缺血通过升高细胞质Ca(2+)使浦肯野细胞的动作电位编码不稳定，而无需谷氨酸参与，这随后导致它们的兴奋性毒性死亡。
