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

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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