非洲爪蟾细胞培养中，内源性释放的三磷酸腺苷对发育中神经肌肉突触自发递质分泌的增强作用。

Potentiation by endogenously released ATP of spontaneous transmitter secretion at developing neuromuscular synapses in Xenopus cell cultures.

作者信息

Fu W M, Huang F L

机构信息

Pharmacological Institute, College of Medicine, National Taiwan University, Taipei.

出版信息

Br J Pharmacol. 1994 Mar;111(3):880-6. doi: 10.1111/j.1476-5381.1994.tb14820.x.

DOI:10.1111/j.1476-5381.1994.tb14820.x

PMID:8019765

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1910076/

Abstract

Previously we have shown that extracellular application of ATP, a substance co-stored and co-released with acetylcholine (ACh) in the peripheral nervous system, markedly potentiated the frequency of spontaneous synaptic currents (SSCs) produced by ACh. In the present study, we have further characterized the purinoceptor which mediates the potentiation effect of ATP and the role of endogenously released ATP. 2. Pretreatment with a P2-purinoceptor antagonist, suramin (0.3 mM), but not a P1-purinoceptor antagonist, 8-phenyltheophylline (0.1 mM), prevented the potentiating effect of ATP. 3. We studied the role of endogenously released ATP by examining the effect of a specific P2-purinoceptor antagonist on the frequency of spontaneous synaptic events at high-activity synapses (> or = 3 Hz) and found that suramin, but not 8-phenyltheophylline markedly reduced the frequency of SSCs at these high-activity synapses. In addition, desensitizing the P2-purinoceptor with alpha,beta-methylene ATP also produced similar effects to suramin. 4. Extracellular application of the L-type Ca2+ channel blockers, verapamil, nifedipine or diltiazem (10 microM each) reduced SSC frequency of high-activity synapses, while the N-type Ca2+ channel blocker, omega-conotoxin had no appreciable effect. The potentiating effect of ATP was further prevented by pretreatment with the L-type Ca2+ channel blockers. On the other hand, Bay K 8644, which is a depolarization-dependent L-type Ca2+ channel agonist, potentiated SSC frequency at these high-activity synapses. 5. These results suggest that endogenous release of ATP at developing neuromuscular synapses is responsible for the maintenance of high levels of spontaneous ACh release, which is known to play a crucial role in regulating postsynaptic differentiation.

摘要

先前我们已经表明，在周围神经系统中，与乙酰胆碱（ACh）共同储存和共同释放的物质ATP的细胞外应用，显著增强了由ACh产生的自发突触电流（SSCs）的频率。在本研究中，我们进一步对介导ATP增强作用的嘌呤受体以及内源性释放的ATP的作用进行了表征。2. 用P2嘌呤受体拮抗剂苏拉明（0.3 mM）预处理可阻止ATP的增强作用，但用P1嘌呤受体拮抗剂8-苯基茶碱（0.1 mM）预处理则不能。3. 我们通过检查特定P2嘌呤受体拮抗剂对高活性突触（≥3 Hz）处自发突触事件频率的影响，研究了内源性释放的ATP的作用，发现苏拉明而非8-苯基茶碱显著降低了这些高活性突触处的SSCs频率。此外，用α,β-亚甲基ATP使P2嘌呤受体脱敏也产生了与苏拉明类似的效果。4. 细胞外应用L型钙通道阻滞剂维拉帕米、硝苯地平或地尔硫䓬（各10 μM）可降低高活性突触的SSC频率，而N型钙通道阻滞剂ω-芋螺毒素则没有明显作用。L型钙通道阻滞剂预处理可进一步阻止ATP的增强作用。另一方面，作为去极化依赖性L型钙通道激动剂的Bay K 8644增强了这些高活性突触处的SSC频率。5. 这些结果表明，在发育中的神经肌肉突触处内源性释放的ATP负责维持高水平的自发ACh释放，而自发ACh释放已知在调节突触后分化中起关键作用。