Elliott E M, Malouf A T, Catterall W A
Department of Pharmacology, University of Washington, Seattle 98195, USA.
J Neurosci. 1995 Oct;15(10):6433-44. doi: 10.1523/JNEUROSCI.15-10-06433.1995.
Multiple subtypes of voltage-gated calcium channels are differentially localized in brain neurons suggesting that they serve distinct roles in neuronal excitation and signaling. In organotypic hippocampal slice cultures, class D (L-type) calcium channels are predominantly located in the cell bodies of CA3 neurons while class B (N-type) and class A (P or Q-type) are localized in dendrites and associated presynaptic terminals with relatively low somal expression. Using specific antagonists to inhibit calcium transients recorded in CA3 neuronal cell bodies, we found that L-type calcium channels have a predominant role in somal calcium transients elicited by trains of strong stimuli applied to either the soma or the distal apical dendrite while class A calcium channels make a smaller contribution. Presynaptic class B (N-type) and class A (P- and/or Q-type) calcium channels are critical for glutamate-mediated synaptic transmission onto the dendrites of CA3 neurons. Postsynaptic class A and B calcium channels detected on the dendritic shaft by immunocytochemistry were not found to contribute substantially to somal calcium transients during repetitive stimulation of distal dendrites, but sodium channels were required for calcium transients elicited by somatic or dendritic stimulation. Our results show that the different calcium channel subtypes serve distinct roles in cellular activation and transmission of signals in CA3 neurons, consistent with their differential subcellular localization.
电压门控钙通道的多种亚型在脑神经元中呈差异定位,这表明它们在神经元兴奋和信号传导中发挥着不同的作用。在器官型海马切片培养物中,D类(L型)钙通道主要位于CA3神经元的细胞体中,而B类(N型)和A类(P或Q型)则定位于树突及相关的突触前终末,在细胞体中的表达相对较低。使用特异性拮抗剂抑制在CA3神经元细胞体中记录到的钙瞬变,我们发现L型钙通道在由施加于细胞体或远端顶端树突的强刺激序列引发的细胞体钙瞬变中起主要作用,而A类钙通道的作用较小。突触前B类(N型)和A类(P和/或Q型)钙通道对于谷氨酸介导的向CA3神经元树突的突触传递至关重要。通过免疫细胞化学在树突轴上检测到的突触后A类和B类钙通道在重复刺激远端树突期间对细胞体钙瞬变的贡献不大,但细胞体或树突刺激引发的钙瞬变需要钠通道。我们的结果表明,不同的钙通道亚型在CA3神经元的细胞激活和信号传递中发挥着不同的作用,这与其亚细胞定位的差异一致。