MODULATION OF CA++ ENTRY IN HIPPOCAMPAL NEURONS

海马神经元 CA 进入的调节

• 批准号: 3416793
• 负责人: RICHARD A. GRAY
• 金额: $ 1.79万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-30 至 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3416793
• 关键词: NMDA receptors; calcium channel; calcium channel blockers; calcium flux; fiber cell; granule cell; guinea pigs; neurons; pyramidal cells; synapses; voltage /patch clamp

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.

神经元中钙的进入和积聚涉及几种细胞 过程，包括直接控制电反应性;间接 通过激活其他离子电导来控制膜电位; 酶系统的细胞内控制;以及 突触传递的可塑性 调节Ca 2+进入和 因此，神经元中的积累可能会对神经元的许多方面产生影响。 细胞功能 这项提议旨在扩大β-肾上腺素能和 毒蕈碱胆碱能激动剂调节电压门控钙通道 豚鼠海马颗粒细胞和CA 3区锥体细胞 CA 1锥体细胞Ca ~（2+）通道调控的研究 神经元和苔藓纤维突触前末梢。 有越来越多的建议，激活NMDA类的， 谷氨酸受体可能影响电压门控性Ca ~（2+）通道。 实验 这里提出的解决一些基本问题， NMDA受体和电压门控Ca 2+通道的相互作用。 如果 发现细胞内Ca 2+水平增加，这是由Ca 2+引起的， 通过NMDA门控通道或其他方式进入，可导致随后的 Ca 2+通道活性增加，这可能具有重要意义 for neuronal神经function功能. 几种病理状况会导致 Ca 2+积累增加，如缺氧或癫痫发作活动， 通过Ca 2+流入的这种正反馈机制加剧。 突触前电压门控钙通道的钙内流 终端被认为是启动的必要的第一步， 中枢神经系统中几乎所有突触都释放神经递质 系统 虽然体细胞钙通道的特性已经被 在许多准备工作中描述，几乎没有直接证据支持 体细胞和突触末端钙通道具有 相似的属性。 这一假设将直接通过比较 苔藓纤维突触终末钙通道的特性， 在细胞体中产生末端齿状颗粒的那些 细胞，以及海马中的其他主要细胞类型。