Stephens Gary J
School of Pharmacy, The University of Reading, Hopkins Building, Whiteknights, Reading, RG6 6UB, UK.
Trends Pharmacol Sci. 2009 Aug;30(8):421-30. doi: 10.1016/j.tips.2009.05.008. Epub 2009 Jul 24.
Throughout the central nervous system a dominant form of inhibition of neurotransmitter release from presynaptic terminals is mediated by G-protein-coupled receptors (GPCRs). Neurotransmitter release is typically induced by action potentials (APs), but can also occur spontaneously. Presynaptic inhibition by GPCRs has been associated with modulation of voltage-dependent ion channels. However, electrophysiological recordings of spontaneous, AP-independent (so-called 'miniature') postsynaptic events reveal an additional, important form of GPCR-mediated presynaptic inhibition, distinct from effects on ionic conductances and consistent with a direct action on the vesicle release machinery. Recent studies suggest that such miniature events might be of physiological relevance not only in signalling but also in development. In the cerebellum, neurotransmitter release onto Purkinje cells occurs by AP-dependent and AP-independent pathways. Here, I focus on inhibitory synapses between interneurons and Purkinje cells, which are subject to strong, identifiable regulation by endogenous GPCR agonists, to consider mechanisms of GPCR-mediated presynaptic inhibition.
在整个中枢神经系统中，从突触前终末抑制神经递质释放的主要形式是由G蛋白偶联受体（GPCRs）介导的。神经递质的释放通常由动作电位（APs）诱导，但也可自发发生。GPCRs介导的突触前抑制与电压依赖性离子通道的调节有关。然而，对自发的、不依赖AP（即所谓的“微小”）突触后事件的电生理记录揭示了GPCR介导的突触前抑制的另一种重要形式，这不同于对离子电导的影响，并且与对囊泡释放机制的直接作用一致。最近的研究表明，此类微小事件可能不仅在信号传导中而且在发育过程中都具有生理相关性。在小脑中，神经递质释放到浦肯野细胞上是通过依赖AP和不依赖AP的途径进行的。在这里，我将重点关注中间神经元与浦肯野细胞之间的抑制性突触，这些突触受到内源性GPCR激动剂的强烈且可识别的调节，以探讨GPCR介导的突触前抑制的机制。
