Padua R A, Yamamoto T, Fyda D, Sawchuk M A, Geiger J D, Nagy J I
Departments of Physiology, University of Manitoba, Faculty of Medicine, Winnipeg, Canada.
J Chem Neuroanat. 1992 Jan-Feb;5(1):63-73. doi: 10.1016/0891-0618(92)90034-n.
Quantitative and qualitative autoradiographic methods together with lesion approaches were used to determine the distribution of [3H]ryanodine binding sites in rat brain and the neuronal localization of these sites in the hippocampus. In normal animals, levels of [3H]ryanodine binding sites ranged from a low of about 1 fmol/mg tissue in subcortical structures to a high of 12-18 fmol/mg tissue in subregions of the hippocampus and the olfactory bulb. Relatively high densities of sites (5-9 fmol/mg tissue) were also seen in the olfactory tubercle, most areas of the cerebral cortex, accumbens nucleus, striatum, lateral septal nuclei, pontine nucleus, superior colliculus and granule cell layer of the cerebellum. Specific binding was undetectable in white matter. In experimental animals, intracerebral injections of kainic acid caused neuronal degeneration and a near total depletion of [3H]ryanodine binding sites in the dentate gyrus and in fields CA1, CA2 and CA3 of the hippocampus. Injections of kainic acid that left dentate granule cells largely intact while destroying all neurons in field CA3 had no effect on binding sites in the dentate gyrus. However, these lesions substantially reduced the density of binding in field CA3, leaving a narrow band of sites outlining the position of the degenerated CA3 pyramidal cells. Mechanical knife-cut lesions that severed the granule cell mossy fiber input to field CA3 reduced the density of binding sites in the CA3 region. The results indicate that [3H]ryanodine binding sites in brain are heterogeneously distributed and suggest that a proportion of these sites in the hippocampus may be contained in mossy fiber terminals where a presumptive calcium channel/ryanodine receptor complex may be involved in the regulation of calcium mobilization and/or neurotransmitter release.
采用定量和定性放射自显影方法以及损伤方法来确定大鼠脑中[³H]ryanodine结合位点的分布以及这些位点在海马体中的神经元定位。在正常动物中，[³H]ryanodine结合位点的水平范围从皮质下结构中约1 fmol/mg组织的低水平到海马体和嗅球亚区域中12 - 18 fmol/mg组织的高水平。在嗅结节、大脑皮质的大多数区域、伏隔核、纹状体、外侧隔核、脑桥核、上丘以及小脑颗粒细胞层中也观察到相对较高密度的位点（5 - 9 fmol/mg组织）。在白质中未检测到特异性结合。在实验动物中，脑内注射红藻氨酸导致神经元变性以及海马体齿状回和CA1、CA2和CA3区中[³H]ryanodine结合位点几乎完全耗竭。注射红藻氨酸使齿状颗粒细胞基本完整而破坏CA3区所有神经元，对齿状回中的结合位点没有影响。然而，这些损伤显著降低了CA3区的结合密度，留下一条狭窄的位点带勾勒出退化的CA3锥体细胞的位置。切断颗粒细胞苔藓纤维输入到CA3区的机械刀割损伤降低了CA3区结合位点的密度。结果表明，脑中的[³H]ryanodine结合位点分布不均，提示海马体中这些位点的一部分可能存在于苔藓纤维终末，推测钙通道/ryanodine受体复合物可能参与钙动员和/或神经递质释放的调节。
