Instituto Teófilo Hernando, Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, Arzobispo Morcillo, 4, 28029, Madrid, Spain.
Pflugers Arch. 2018 Jan;470(1):53-60. doi: 10.1007/s00424-017-2064-1. Epub 2017 Sep 2.
The coexistence of different subtypes of voltage-dependent calcium channels (VDCC) within the same chromaffin cell (CC) and the marked interspecies variability in the proportion of VDCC subtypes that are present in the plasmalemma of the CCs raises the question on their roles in controlling different physiological functions. Particularly relevant seems to be the role of VDCCs in the regulation of the exocytotic neurotransmitter release process, and its tightly coupled membrane retrieval (endocytosis) process since both are Ca-dependent processes. This review is focused on the role of Ca influx through L-type VDCC in the regulation of these two processes. It is currently accepted that the different VDCC subtypes (i.e., T, L, N, P/Q, R) contribute to exocytosis proportionally to their density of expression and gating properties. However, the pattern of stimulation defines a preferential role of the different subtypes of VDCC on exocytosis and endocytosis. Thus, L-type channels seem to control catecholamine release induced by prolonged stimuli while fast exocytosis in response to short square depolarizing pulses or action potentials is mediated by Ca entering CCs through P/Q channels. The pattern of stimulation also influences the endocytotic process, and thus, electrophysiological data suggest the sustained Ca entry through slow-inactivating L-type channels could be responsible for the activation of fast endocytosis.
同一嗜铬细胞(CC)内存在不同亚型的电压依赖性钙通道(VDCC),而且不同物种的 CC 质膜中存在的 VDCC 亚型比例存在明显的种间变异性,这引发了关于它们在控制不同生理功能中的作用的问题。VDCC 在调节胞吐作用的神经递质释放过程及其紧密偶联的膜回收(内吞作用)过程中的作用似乎尤为重要,因为这两个过程都是 Ca 依赖性的。本综述重点介绍 L 型 VDCC 通过 Ca 内流在调节这两个过程中的作用。目前人们普遍认为,不同的 VDCC 亚型(即 T、L、N、P/Q、R)通过其表达密度和门控特性按比例促进胞吐作用。然而,刺激模式定义了不同亚型的 VDCC 对胞吐作用和内吞作用的优先作用。因此,L 型通道似乎控制着由长时间刺激引起的儿茶酚胺释放,而响应短平方去极化脉冲或动作电位的快速胞吐作用则由通过 P/Q 通道进入 CC 的 Ca 介导。刺激模式也会影响内吞作用过程,因此,电生理数据表明,通过缓慢失活的 L 型通道持续的 Ca 内流可能负责激活快速内吞作用。