Acid-Sensing Properties in Rat Gastric Sensory Neurons from Normal and Ulcerated Stomach
Acid-Sensing Properties in Rat Gastric Sensory Neurons from Normal and Ulcerated Stomach
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DOI：
10.1523/jneurosci.2894-04.2005
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发表时间：
2005-03
期刊：
影响因子：
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通讯作者：
T. Sugiura;K. Dang;K. Lamb;K. Bielefeldt;G. Gebhart
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文献类型：
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作者：
T. Sugiura;K. Dang;K. Lamb;K. Bielefeldt;G. Gebhart
胃酸导致近端胃肠道疾病患者的消化不良症状，包括腹痛。为了研究胃酸化学感受的分子传感器(S)，我们研究了支配胃的背根节和结状神经节神经元的酸诱发电流，并观察了胃溃疡诱导后它们的调制。将荧光染料(DiI)注入胃壁，逆行标记胃感觉神经元。1~2周后，将45只S胃腔暴露于60%醋酸灌胃远端夹闭区域，造成胃溃疡；对照组给予生理盐水。在全细胞电压钳记录中，所有胃背根神经节神经元和55%的NG神经元均出现一过性、阿米洛利敏感、酸敏的离子通道电流。在其余45%的NG神经元中，质子激活了一种缓慢而持续的电流，该电流被瞬时受体电位香草素1型拮抗剂卡萨西平所减弱。NG和DRG神经元对阿米洛利敏感的ASIC电流的动力学和质子敏感性不同。NG神经元具有较低的质子敏感性和较快的动力学，提示胃的迷走神经和内脏神经支配中有特定亚型ASICs的表达。锌离子和N，N，N‘，N’-四-(2-吡啶甲基)-乙二胺对酸诱导电流的影响提示ASIC1a和ASIC2a亚基的作用。胃溃疡通过增加胃背根神经节神经元的pH敏感性和电流密度，改变胃DRG神经元的电流动力学，从而改变酸诱发电流的特性。NG和DRG神经元的不同特性及其在损伤后的调节表明迷走神经和脊髓传入神经元在化学感觉和化学伤害感受中的不同贡献。
Gastric acid contributes to dyspeptic symptoms, including abdominal pain, in patients with disorders of the proximal gastrointestinal tract. To examine the molecular sensor(s) of gastric acid chemonociception, we characterized acid-elicited currents in dorsal root ganglion (DRG) and nodose ganglion (NG) neurons that innervate the stomach and examined their modulation after induction of gastric ulcers. A fluorescent dye (DiI) was injected into the stomach wall to retrogradely label gastric sensory neurons. After 1-2 weeks, gastric ulcers were induced by 45 s of luminal exposure of the stomach to 60% acetic acid injected into a clamped area of the distal stomach; control animals received saline. In whole-cell voltage-clamp recordings, all gastric DRG neurons and 55% of NG neurons exhibited transient, amiloride-sensitive, acid-sensing ion-channel (ASIC) currents. In the remaining 45% of NG neurons, protons activated a slow, sustained current that was attenuated by the transient receptor potential vanilloid subtype 1 antagonist, capsazepine. The kinetics and proton sensitivity of amiloride-sensitive ASIC currents differed between NG and DRG neurons. NG neurons had a lower proton sensitivity and faster kinetics, suggesting expression of specific subtypes of ASICs in the vagal and splanchnic innervation of the stomach. Effects of Zn2+ and N,N,N′,N′-tetrakis-(2-pyridylmethyl)-ethylenediamine on acid-elicited currents suggest contributions of ASIC1a and ASIC2a subunits. Gastric ulcers altered the properties of acid-elicited currents by increasing pH sensitivity and current density and changing current kinetics in gastric DRG neurons. The distinct properties of NG and DRG neurons and their modulation after injury suggest differential contributions of vagal and spinal afferent neurons to chemosensation and chemonociception.