Takemura M, Kiyama H, Fukui H, Tohyama M, Wada H
Department of Pharmacology II, Osaka University School of Medicine, Japan.
Neuroscience. 1989;32(2):405-16. doi: 10.1016/0306-4522(89)90089-4.
The distribution of [125I]omega-conotoxin GVIA binding sites, the putative voltage-sensitive calcium channels, was studied by an autoradiographic method in the rat brain. The toxin binding sites were distributed throughout the brain in a highly heterogeneous manner. The highest density of the binding sites was observed in the cerebral cortex, hippocampus, amygdaloid complex, substantia nigra, caudate putamen, superior colliculus, nucleus of the solitary tract, and the dorsal horn of the cervical spine. The glomerular layer of the olfactory bulb, molecular layer of the cerebellar cortex, and posterior lobe of the hypophysis showed intermediate density but the density was higher than in the surrounding areas. The globus pallidus, thalamic areas, inferior olive, and pontine nuclei showed low density, while no binding sites were observed in the white matter tract regions such as the internal and external capsule, corpus callosum, fimbria of the hippocampus, fornix, stria medullaris of the thalamus, and fasciculus retroflexus. This distribution of omega-conotoxin binding sites indicates that the toxin binding sites are localized in those areas of the brain enriched in synaptic connections. This distribution pattern resembles that reported for voltage-sensitive sodium channels but it differs from that of the binding sites of dihydropyridines and verapamil. These results suggest that omega-conotoxin recognizes different molecules from organic calcium channel antagonist binding sites and that omega-conotoxin-sensitive voltage-sensitive calcium channels are concentrated in the synaptic zones and play a key role in the excitation-secretion coupling of neurotransmitters.
采用放射自显影法研究了大鼠脑中[125I]ω-芋螺毒素GVIA结合位点(即推测的电压敏感性钙通道)的分布。毒素结合位点在脑中以高度不均一的方式分布。在大脑皮层、海马、杏仁复合体、黑质、尾状壳核、上丘、孤束核以及颈髓背角观察到最高密度的结合位点。嗅球的肾小球层、小脑皮层分子层以及垂体后叶显示中等密度,但该密度高于周围区域。苍白球、丘脑区域、下橄榄核和脑桥核显示低密度,而在白质束区域如内囊和外囊、胼胝体、海马伞、穹窿、丘脑髓纹和后屈束未观察到结合位点。ω-芋螺毒素结合位点的这种分布表明,毒素结合位点定位于脑内富含突触连接的那些区域。这种分布模式类似于报道的电压敏感性钠通道的分布模式,但不同于二氢吡啶和维拉帕米结合位点的分布模式。这些结果表明,ω-芋螺毒素识别的分子不同于有机钙通道拮抗剂结合位点识别的分子,并且ω-芋螺毒素敏感的电压敏感性钙通道集中在突触区,在神经递质的兴奋-分泌偶联中起关键作用。