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The Participation of Endocannabinoid Receptors in the Regulation of Spontaneous Synaptic Activity at Neuromuscular Junctions of Mice
Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology ( IF 1.1 ) Pub Date : 2020-01-01 , DOI: 10.1134/s1990747819060059
A. E. Gaydukov , I. Z. Dzhalagoniya , E. O. Tarasova , O. P. Balezina

Abstract The mechanisms underlying changes in spontaneous release of acetylcholine (ACh) induced by exogenous agonists and antagonists of endocannabinoid receptors were investigated by recording miniature endplate potentials (MEPPs) in motor synapses of mouse diaphragm preparations with intracellular microelectrodes. There have not been observed any statistically significant changes either in the membrane potential of muscle fibers or in the frequency, amplitude, and time parameters of the MEPPs under the action of AM-251 (1 μM), antagonist/inverse agonist of CB1 receptors, for 60 min. Activation of CB receptors by their exogenous agonist WIN 55,212-2 (WIN) (20 μM) for 1 h did not cause statistically significant changes in the amplitude of the MEPPs. However, MEPP frequency increased by more than 50% as compared to the control under the action of WIN for 30–60 min. Blocking of CB1 receptors by AM-251 (1 μM) prevented the WIN-induced increase in MEPP frequency. A protein kinase A inhibitor H-89 (1 μM) did not prevent the enhancement of the ACh secretion upon activation of CB receptors by WIN. WIN lost the ability to increase MEPP frequency in the presence of a phospholipase C inhibitor U73122 (5 μM), which did not affect by itself the amplitude and temporal characteristics or MEPP frequency. A protein kinase C inhibitor, chelerythrin (4 μM) or ryanodine, which blocks the ryanodine receptors (RyRs) at a concentration of 5 μM, also prevented the WIN-induced increase in MEPP frequency. Thus, a signaling cascade triggered by stimulation of presynaptic CB1 receptors with subsequent activation of phospholipase C, protein kinase C, and the release of stored calcium, leading to an increase in the frequency of spontaneous quantal release of ACh, has been detected for the first time in mouse motor synapses. This suggests the presence of CB1 receptors on the presynaptic membrane in mouse motor nerve terminals and the possibility of activation of these receptors by endocannabinoids for potentiating the spontaneous secretion of ACh.

中文翻译:

内源性大麻素受体参与调节小鼠神经肌肉接头处的自发突触活动

摘要 通过使用细胞内微电极记录小鼠隔膜制剂的运动突触中的微型终板电位 (MEPP),研究了内源性大麻素受体激动剂和拮抗剂引起的乙酰胆碱 (ACh) 自发释放变化的潜在机制。在 CB1 受体拮抗剂/反向激动剂 AM-251 (1 μM) 的作用下,肌肉纤维的膜电位或 MEPP 的频率、幅度和时间参数均未观察到任何统计学上的显着变化, 60 分钟。CB 受体通过其外源激动剂 WIN 55,212-2 (WIN) (20 μM) 激活 1 小时不会导致 MEPP 幅度的统计学显着变化。然而,在 WIN 作用下 30-60 分钟,与对照相比,MEPP 频率增加了 50% 以上。AM-251 (1 μM) 对 CB1 受体的阻断阻止了 WIN 诱导的 MEPP 频率增加。蛋白激酶 A 抑制剂 H-89 (1 μM) 不会阻止 WIN 激活 CB 受体后 ACh 分泌的增强。在存在磷脂酶 C 抑制剂 U73122 (5 μM) 的情况下,WIN 失去了增加 MEPP 频率的能力,这本身不影响振幅和时间特性或 MEPP 频率。蛋白激酶 C 抑制剂白屈菜红素 (4 μM) 或兰尼碱在 5 μM 的浓度下阻断兰尼碱受体 (RyRs),也阻止了 WIN 诱导的 MEPP 频率增加。因此,由刺激突触前 CB1 受体触发的信号级联反应,随后激活磷脂酶 C、蛋白激酶 C 和释放储存的钙,导致 ACh 自发量子释放的频率增加,这是首次在小鼠运动突触。这表明小鼠运动神经末梢突触前膜上存在 CB1 受体,以及内源性大麻素激活这些受体以增强乙酰胆碱的自发分泌的可能性。
更新日期:2020-01-01
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