INSERM U901, Institut de Neurobiologie de la Méditerranée Marseille, France.
Front Mol Neurosci. 2011 Jul 28;4:13. doi: 10.3389/fnmol.2011.00013. eCollection 2011.
Endocannabinoids are known as retrograde messengers, being released from the postsynaptic neuron and acting on specific presynaptic G-protein-coupled cannabinoid (CB) receptors to decrease neurotransmitter release. Also, at physiologically relevant concentrations cannabinoids can directly modulate the function of voltage-gated and receptor-operated ion channels. Using patch-clamp recording we analyzed the consequences of the direct action of an endocannabinoid, 2-arachidonoylglycerol (2-AG), on the functional properties of glycine receptor channels (GlyRs) and ionic currents in glycinergic synapses. At physiologically relevant concentrations (0.1-1 μM), 2-AG directly affected the functions of recombinant homomeric α1H GlyR: it inhibited peak amplitude and dramatically enhanced desensitization. The action of 2-AG on GlyR-mediated currents developed rapidly, within ∼300 ms. Addition of 1 μM 2-AG strongly facilitated the depression of glycine-induced currents during repetitive (4-10 Hz) application of short (2 ms duration) pulses of glycine to outside-out patches. In brainstem slices from CB1 receptor knockout mice, 2-AG significantly decreased the extent of facilitation of synaptic currents in hypoglossal motoneurons during repetitive (10-20 Hz) stimulation. These observations suggest that endocannabinoids can modulate postsynaptic metaplasticity of glycinergic synaptic currents in a CB1 receptor-independent manner.
内源性大麻素作为逆行信使，从突触后神经元释放出来，并作用于特定的突触前 G 蛋白偶联大麻素（CB）受体，以减少神经递质的释放。此外，在生理相关浓度下，大麻素可以直接调节电压门控和受体操纵的离子通道的功能。我们使用膜片钳记录技术分析了内源性大麻素 2-花生四烯酸甘油（2-AG）对甘氨酸受体通道（GlyRs）和糖基化突触中离子电流的功能特性的直接作用的后果。在生理相关浓度（0.1-1μM）下，2-AG 直接影响重组同型 α1H GlyR 的功能：它抑制峰幅度并显著增强脱敏。2-AG 对 GlyR 介导电流的作用在约 300ms 内迅速发展。添加 1μM 2-AG 可强烈促进重复（4-10Hz）应用短（2ms 持续时间）甘氨酸脉冲时甘氨酸诱导电流的抑制。在 CB1 受体敲除小鼠的脑桥切片中，2-AG 可显著减少重复（10-20Hz）刺激下舌下运动神经元突触电流的易化程度。这些观察结果表明，内源性大麻素可以以 CB1 受体非依赖性方式调节甘氨酸能突触电流的突触后代谢性。
