Institute of experimental and clinical Pharmacology, Medical University of Graz, Universitätsplatz 4, 8010 Graz, Austria.
Curr Mol Pharmacol. 2008 Jun;1(2):106-29. doi: 10.2174/1874467210801020106.
Neurons communicate through the exocytotic release of transmitters from presynaptic axon terminals and the ensuing activation of postsynaptic receptors. Instantaneous responses of postsynaptic cells to released neurotransmitters are mediated by ligand-gated ion channels, whereas G protein-coupled receptors mediate rather delayed effects. Moreover, the actions of ionotropic receptors are transient (milliseconds to seconds) and those of G protein-coupled receptors are more long lasting (seconds to minutes). Accordingly, neuronal signalling via ligand-gated ion channels is termed neurotransmission, whereas signalling via G protein-coupled receptors is termed neuromodulation. Exocytotic transmitter release is modulated by a variety of mechanisms such as previous activity at the synapse and the presence of extracellular neurotransmitters. Like the postsynaptic responses, presynaptic modulation is not only mediated by slowly acting G protein-coupled receptors, but also by fast acting ligand-gated ion channels. Accordingly, members of all known families of ligand-gated ion channels (cys-loop receptors, such as GABA(A), glycine, nicotinic acetylcholine, and 5-HT(3) receptors, ionotropic glutamate receptors, P2X receptors, and vanilloid receptors) are known to control transmitter release. All these ligand-gated ion channels display heterogeneous structures and functions. Therefore, activation of such presynaptic receptors can control transmitter release in different ways and through a multitude of mechanisms. This review provides a summary of the functions of the different presynaptic ligand-gated ion channels and presents prototypic examples for the physiological and pharmacological relevance of these presynaptic receptors.
神经元通过突触前轴突末梢的胞吐作用释放递质，并激活随后的突触后受体来进行通讯。突触后细胞对释放的神经递质的瞬时反应是由配体门控离子通道介导的，而 G 蛋白偶联受体介导的则是相当延迟的效应。此外，离子型受体的作用是短暂的（毫秒到秒），而 G 蛋白偶联受体的作用持续时间更长（秒到分钟）。因此，通过配体门控离子通道的神经元信号传递称为神经递质传递，而通过 G 蛋白偶联受体的信号传递称为神经调质传递。胞吐递质释放受多种机制的调节，如突触前的先前活动和细胞外神经递质的存在。与突触后反应一样，突触前调制不仅由缓慢作用的 G 蛋白偶联受体介导，也由快速作用的配体门控离子通道介导。因此，所有已知配体门控离子通道家族（环状受体，如 GABA(A)、甘氨酸、烟碱型乙酰胆碱和 5-HT(3)受体、离子型谷氨酸受体、P2X 受体和香草素受体）的成员都被认为可以控制递质释放。所有这些配体门控离子通道都具有异质的结构和功能。因此，激活这些突触前受体可以通过多种机制以不同的方式控制递质释放。这篇综述总结了不同突触前配体门控离子通道的功能，并介绍了这些突触前受体在生理和药理学方面的典型实例。
