Koussoulas Katerina, Swaminathan Mathusi, Fung Candice, Bornstein Joel C, Foong Jaime P P
Department of Physiology, University of Melbourne, Parkville, VIC, Australia.
Front Physiol. 2018 Feb 13;9:97. doi: 10.3389/fphys.2018.00097. eCollection 2018.
γ-Aminobutyric Acid (GABA) and its receptors, GABA, are expressed in several locations along the gastrointestinal tract. Nevertheless, a role for GABA in enteric synaptic transmission remains elusive. In this study, we characterized the expression and function of GABA in the myenteric plexus of the mouse ileum. About 8% of all myenteric neurons were found to be GABA-immunoreactive (GABA+) including some Calretinin+ and some neuronal nitric oxide synthase (nNOS+) neurons. We used mice, which express a genetically encoded fluorescent calcium indicator in all enteric neurons and glia. Exogenous GABA increased the intracellular calcium concentration, [Ca] of some myenteric neurons including many that did not express GABA or nNOS (the majority), some GABA+, Calretinin+ or Neurofilament-M (NFM)+ but rarely nNOS+ neurons. GABA+ terminals contacted a significantly larger proportion of the cell body surface area of Calretinin+ neurons than of nNOS+ neurons. Numbers of neurons with GABA-induced [Ca] transients were reduced by GABA and nicotinic receptor blockade. Electrical stimulation of interganglionic fiber tracts was used to examine possible effects of endogenous GABA release. [Ca] transients evoked by single pulses were unaffected by specific antagonists for each of the 3 GABA receptor subtypes. [Ca] transients evoked by 20 pulse trains were significantly amplified by GABA receptor blockade. These data suggest that GABA and GABA receptors are not involved in synaptic transmission, but suggest a novel role for GABA receptors in modulating slow synaptic transmission, as indicated by changes in [Ca] transients, within the ENS.
γ-氨基丁酸（GABA）及其受体GABA在胃肠道的多个部位均有表达。然而，GABA在肠内突触传递中的作用仍不明确。在本研究中，我们对小鼠回肠肌间神经丛中GABA的表达及功能进行了表征。发现所有肌间神经元中约8%为GABA免疫反应阳性（GABA+），包括一些钙视网膜蛋白阳性（Calretinin+）神经元和一些神经元型一氧化氮合酶（nNOS+）神经元。我们使用了在所有肠神经元和神经胶质细胞中均表达一种基因编码荧光钙指示剂的小鼠。外源性GABA可增加一些肌间神经元的细胞内钙浓度[Ca]，这些神经元包括许多不表达GABA或nNOS的神经元（大多数）、一些GABA+、钙视网膜蛋白+或神经丝-M（NFM）+神经元，但很少包括nNOS+神经元。GABA+终末与钙视网膜蛋白+神经元的细胞体表面积接触的比例明显大于与nNOS+神经元的接触比例。GABA诱导的[Ca]瞬变的神经元数量因GABA和烟碱受体阻断而减少。使用神经节间纤维束的电刺激来检查内源性GABA释放的可能影响。单个脉冲诱发的[Ca]瞬变不受3种GABA受体亚型中任何一种的特异性拮抗剂的影响。20个脉冲串诱发的[Ca]瞬变因GABA受体阻断而显著放大。这些数据表明，GABA和GABA受体不参与突触传递，但表明GABA受体在调节肠神经系统内由[Ca]瞬变变化所指示的缓慢突触传递中具有新的作用。
