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

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中，CNQX抑制了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

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