MODULATION OF CA++ ENTRY IN HIPPOCAMPAL NEURONS

钙离子在神经元中的进入和积聚涉及多个细胞 进程，包括直接控制电响应性；间接 通过激活其他离子电导来控制膜电位； 神经递质释放；酶系统的细胞内控制；以及 突触传递的可塑性。钙离子内流和钙离子通道的调控 因此，神经元中的积聚可能会对以下许多方面产生影响 细胞功能。 这项提案旨在扩大研究结果，即β-肾上腺素能和 M胆碱能激动剂对电压门控性钙通道的调节作用 豚鼠海马区颗粒细胞和CA3锥体细胞 CA1区锥体细胞钙通道调制的形成与研究 神经元和苔藓纤维突触前终末。 越来越多的人认为，NMDA类分子的激活 谷氨酸受体可能影响电压门控性钙通道。这些实验 这里提出的建议解决了一些基本的问题，即 NMDA受体与电压门控钙通道的相互作用如果是的话 发现细胞内钙离子水平的升高，要么是由钙离子引起的 通过NMDA门控通道或其他方式进入可能会导致后续 钙通道活性增加，这可能具有重大意义 用于神经元功能。几种病理情况会导致 钙离子蓄积增加，如缺氧或癫痫发作活动 这种钙离子内流的正反馈机制加剧了这一现象。 突触前电压门控钙通道的钙内流 终点站被认为是启动 中枢神经几乎所有突触的神经递质释放 系统。尽管体细胞钙通道的特性已经被 在许多制剂中描述，几乎没有直接证据支持 体细胞和突触终末钙通道存在的假设 相似的属性。这一假设将通过比较直接进行检验。 苔藓纤维突触终末钙通道的特性 在细胞体中形成末端齿状颗粒的那些 细胞，以及海马体中的其他主要细胞类型。

Calcium entry and accumulation in neurons are involved in several cellular processes, including direct control of electroresponsiveness; indirect control of membrane potential by activation of other ionic conductances; neurotransmitter release; intracellular control of enzyme systems; and plasticity of synaptic transmission. Modulation of Ca2+ entry and accumulation in neurons, therefore, may have effects on many facets of cellular function. This proposal is aimed at extending findings that beta-adrenergic and muscarinic cholinergic agonists modulate voltage-gated Ca2+ channels in granule cells and CA3 pyramidal cells in the guinea-pig hippocampal formation to the investigation of Ca2+-channel modulation in CA1 pyramidal neurons and mossy-fiber presynaptic terminals. There have been increasing suggestions that activation of the NMDA class of glutamate receptor may affect voltage-gated Ca2+ channels. The experiments proposed here address some fundamental questions about possible interactions of NMDA receptors and voltage-gated Ca2+ channels. If it is found that increased levels of intracellular Ca2+, caused either by Ca2+ entry through NMDA-gated channels or other means, can lead to a subsequent increase in Ca2+-channel activity, this could have significant implications for neuronal function. Several pathological conditions that cause increased Ca2+ accumulation such as anoxia or seizure activity could be exacerbated by such a positive feedback mechanism of Ca2+ influx. Calcium entry through voltage-gated calcium channels at presynaptic terminals is believed to be the requisite first step in the initiation of neurotransmitter release at virtually all synapses in the central nervous system. Although the properties of somatic calcium channels have been described in many preparations, there is little direct evidence supporting the hypothesis that somatic and synaptic terminal calcium channels have similar properties. This hypothesis will be tested directly by comparing the properties of calcium channels in mossy fiber synaptic terminals to those in the cell body that gives rise to the terminal the dentate granule cell, and to the other principle cell types in the hippocampus.