Westenbroek R E, Ahlijanian M K, Catterall W A
Department of Pharmacology, School of Medicine, University of Washington, Seattle 98195.
Nature. 1990 Sep 20;347(6290):281-4. doi: 10.1038/347281a0.
Integration and processing of electrical signals in individual neurons depend critically on the spatial distribution of ion channels on the cell surface. In hippocampal pyramidal neurons, voltage-sensitive calcium channels have important roles in the control of Ca2(+)-dependent cellular processes such as action potential generation, neurotransmitter release, and epileptogenesis. Long-term potentiation of synaptic transmission in the hippocampal pyramidal cell, a form of neuronal plasticity that is thought to represent a cellular correlate of learning and memory, is dependent on Ca2+ entry mediated by synaptic activation of glutamate receptors that have a high affinity for NMDA (N-methyl(-D-aspartate) and are located in distal dendrites. Stimuli causing long-term potentiation at these distal synapses also cause a large local increase in cytosolic Ca2+ in the proximal regions of dendrites. This increase has been proposed to result from activation of voltage-gated Ca2+ channels. At least four types of voltage-gated Ca2+ channels, designated N, L. T and P, may be involved in these processes. Here we show that L-type Ca2+ channels, visualized using a monoclonal antibody, are located in the cell bodies and proximal dendrites of hippocampal pyramidal cells and are clustered in high density at the base of major dendrites. We suggest that these high densities of L-type Ca2+ channels may serve to mediate Ca2+ entry into the pyramidal cell body and proximal dendrites in response to summed excitatory inputs to the distal dendrites and to initiate intracellular regulatory events in the cell body in response to the same synaptic inputs that cause long-term potentiation at distal dendritic synapses.
单个神经元中电信号的整合与处理关键取决于离子通道在细胞表面的空间分布。在海马锥体神经元中,电压敏感性钙通道在控制依赖Ca2+的细胞过程(如动作电位产生、神经递质释放和癫痫发生)中发挥重要作用。海马锥体细胞中突触传递的长时程增强是一种神经元可塑性形式,被认为代表学习和记忆的细胞关联物,它依赖于由对NMDA(N-甲基-D-天冬氨酸)具有高亲和力且位于远端树突中的谷氨酸受体的突触激活介导的Ca2+内流。在这些远端突触处引起长时程增强的刺激也会导致树突近端区域胞质Ca2+大量局部增加。有人提出这种增加是由电压门控Ca2+通道的激活引起的。至少四种类型的电压门控Ca2+通道,即N型、L型、T型和P型,可能参与这些过程。在这里,我们表明,使用单克隆抗体可视化的L型Ca2+通道位于海马锥体神经元的细胞体和近端树突中,并在主要树突基部高密度聚集。我们认为,这些高密度的L型Ca2+通道可能用于介导Ca2+进入锥体细胞体和近端树突,以响应远端树突的兴奋性输入总和,并在细胞体中启动细胞内调节事件,以响应在远端树突突触处引起长时程增强的相同突触输入。