Effects of ryanodine receptor activation on neurotransmitter release and neuronal cell death following kainic acid-induced status epilepticus
Effects of ryanodine receptor activation on neurotransmitter release and neuronal cell death following kainic acid-induced status epilepticus
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DOI：
10.1016/j.eplepsyres.2005.04.006
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发表时间：
2005-06-01
影响因子：
2.2
通讯作者：
Wakabayashi, K
中科院分区：
文献类型：
--
作者：
Mori, F;Okada, M;Wakabayashi, K
细胞内游离Ca2+浓度的动态变化在各种神经功能中起着至关重要的作用。肌醇1,4,5-三磷酸（IP3）受体（IP3R）和ryanodine （Ry）受体（RyR）参与Ca2+诱导的Ca2+释放（CICR）。最近的研究表明，在kainic acid （KA）诱导的癫痫发作后，3型IP3R在大鼠海马神经元中高度表达，而RyR拮抗剂dantrolene可以减少KA诱导的神经元细胞死亡。我们研究了CICR药物对大鼠海马基底和K+诱发的GABA和谷氨酸释放的ryr相关影响，以及ka诱导癫痫发作后小鼠大脑中ryr mRNA表达的变化。Ry对GABA和谷氨酸释放的刺激作用呈双相浓度依赖性。在基础条件和K+诱发条件下，Ry对GABA释放的浓度-响应曲线的拐点低于谷氨酸释放的拐点，表明ryr相关CICR的过度激活导致GABA能和谷氨酸能传递失衡。ka诱导癫痫发作后，海马CA3区和纹状体中出现脑型RyR mRNA的短暂上调，海马、齿状回和新皮层深层中c-Fos mRNA的信号短暂升高。此后，在这些区域出现了一些单链DNA （ssDNA）免疫反应断裂核的死亡神经元。这些发现表明，细胞内Ca2+通过RyR释放可能是ka诱导的神经元细胞死亡的机制之一。(c) 2005 Elsevier B.V.版权所有
Dynamic changes in intracellular free Ca2+ concentration play a crucial role in various neural functions. The inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) and the ryanodine (Ry) receptor (RyR) are involved in Ca2+-induced Ca2+-release (CICR). Recent studies have shown that type 3 IP3R is highly expressed in rat hippocampal neurons after kainic acid (KA)-induced seizures and that dantrolene, a RyR antagonist, reduces KA-induced neuronal cell death. We investigated the RyR-associated effects of CICR agents on basal and K+-evoked releases of GABA and glutamate in rat hippocampus and the changes in expression of mRNA for RyRs in mouse brain after KA-induced seizures. The stimulatory effect of Ry on releases of GABA and glutamate was concentration-dependent in a biphasic manner. The inflection point in concentration-response curves for Ry on GABA release was lower than that for glutamate in both basal and K+-evoked conditions, suggesting that hyperactivation of RyR-associated CICR produces the imbalance between GABAergic and glutamatergic transmission. Following KA-induced seizures, transient up-regulation of brain-type RyR mRNA was observed in the hippocampal CA3 region and striatum, and signals for c-Fos mRNA increased transiently in the hippocampus, dentate gyrus and deeper layers of the neocortex. Thereafter, some dead neurons with single-stranded DNA (ssDNA) immunoreactive fragmented nuclei appeared in these areas. These findings suggest that intracellular Ca2+ release via the RyR might be one of the mechanisms involved in KA-induced neuronal cell death. (c) 2005 Elsevier B.V. All rights reserved.