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Effects of spatio-temporal changes in intracellular free-calcium concentration in central nerve system on signal transmission and anesthetic action

中枢神经系统细胞内游离钙浓度时空变化对信号传递和麻醉作用的影响

基本信息

批准号：
15390471
负责人：
FUJIWARA Naoshi
金额：
$ 6.66万
依托单位：
Niigata University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

Signal transmissions in the cerebral cortex, hippocampus, trigeminal subnucleus caudalis and spinal cord were spatio-temporally characterized using a high-speed optical imaging technique. (1)Slice preparations of the mouse cerebral cortex were stained with a voltage sensitive dye RH414 or a Ca^<2+> indicator Rhod-2 for fluorescence imaging. Electrical single-pulse stimulation to the layer V evoked transient depolarization in the layer V, and then this excitatory response propagated to the layers II-III and widely expanded in these layers. The excitation in the layers II-III was inhibited by an AMPA/kainate receptor antagonist, CNQX, and a P/Q-type Ca^<2+> channel antagonist, ω-agatoxin IVA. Intracellular Ca^<2+> level elevated in the layer V and layers II-III in response to the stimulation. The Ca^<2+> responses were insensitive to CNQX but were profound inhibited by ω-agatoxin IVA and partially by an NMDA receptor antagonist, MK-801. Thus, excitation propagation in the layers II-III m … More ay be mediated by the post-synaptic AMPA/kainate receptors. Ca^<2+> influx through P/Q-type Ca^<2+> channels may play an important role in an intracellular Ca^<2+> elevation inducing pre-synaptic glutamate release. (2)In hippocampal slices, excitation propagation in the CA1 region was also inhibited by CNQX. Ca^<2+> elevation in response to single-pulse stimulation was not so sensitive to MK-801 or Ca^<2+> antagonists at the same concentrations as applied to the cortical slices. (3)In the trigeminal subnucleus caudalis, both excitation propagation and Ca^<2+> elevations in response to single-pulse stimulation were inhibited by CNQX. The results suggest that processes of the Ca^<2+> elevation by single-pulse stimulation were different among the regions of the central nerve system. (4)Slow excitation propagation expanded to the deeper laminae was elicited by high-frequent pulse-train stimulation to the dorsal root. The propagation was enhanced by iteration of the high-frequent stimulation. This enhanced response may correspond to hyper-excitability known as "wind-up" phenomenon. Less

利用高速光学成像技术对大脑皮层、海马、三叉神经尾侧亚核和脊髓的信号传输进行时空表征。（1）用电压敏感染料RH 414或Ca^2+指示剂Rhod-2对小鼠大脑皮层切片进行染色，以进行荧光成像。电单脉冲刺激V层诱发V层的瞬时去极化，然后这种兴奋性反应传播到II-III层，并在这些层中广泛扩展。AMPA/红藻氨酸受体拮抗剂CNQX和P/Q型Ca^<2+>通道拮抗剂ω-agatoxin IVA可抑制Ⅱ-Ⅲ层的兴奋。细胞内Ca^<2+>水平在第V层和第II-III层中响应于刺激而升高。这种Ca^<2+>反应对CNQX不敏感，但可被ω-蛇毒素IVA和部分NMDA受体拮抗剂MK-801显著抑制。因此，在层II-III中的激发传播可以是 ...更多信息可能由突触后AMPA/红藻氨酸受体介导。通过P/Q型Ca^2+通道的Ca^2+内流可能在细胞内Ca^2+升高诱导突触前谷氨酸释放中起重要作用。(2)In海马脑片CA 1区的兴奋传播也被CNQX抑制。单脉冲刺激引起的Ca^2+升高对MK-801或Ca^2+拮抗剂的敏感性不如皮层切片。(3)In在三叉神经尾侧亚核，CNQX抑制单脉冲刺激引起的兴奋传播和Ca^2+升高。结果表明，单脉冲刺激引起的中枢神经系统各部位Ca^<2+>升高过程不同。（4）高频脉冲串刺激背根可使兴奋向深层缓慢传播。通过高频刺激的迭代来增强传播。这种增强的反应可能对应于被称为“发条”现象的过度兴奋。少