Differential pH and capsaicin responses of Griffonia simplicifolia IB4 (IB4)-positive and IB4-negative small sensory neurons
Differential pH and capsaicin responses of Griffonia simplicifolia IB4 (IB4)-positive and IB4-negative small sensory neurons
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DOI：
10.1016/j.neuroscience.2004.05.041
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发表时间：
2004-01-01
期刊：
影响因子：
3.3
通讯作者：
Priestley, JV
中科院分区：
文献类型：
--
作者：
Liu, M;Willmott, NJ;Priestley, JV
质子在炎症和缺血引起的伤害性感受中起着关键作用，但对不同背根神经节（DRG）神经元的相对敏感性知之甚少。因此，我们研究了大鼠DRG细胞的体外反应，根据它们是否结合Griffonia simplicifolia IB4（IB4），一种凝集素，广泛用于区分两个主要群体的小直径神经元。在电压钳条件下，质子激活的内向电流被发现在大约90%的小DRG神经元，并表现出三种波形之一：瞬时，持续或混合。大多数IB4阳性（IB4+）神经元（63%）产生持续的内向电流，对辣椒平敏感。相比之下，在小的IB4-阴性（IB4-）神经元（69%）中最普遍的波形是包含瞬时和持续成分的混合反应。阿米洛利抑制的瞬态成分，而持续的组件显示了一个变量的敏感性辣椒。我们还发现，更多的IB4+细胞响应辣椒素，平均而言，产生了更大幅度的响应比小IB4-神经元，符合其较高的患病率和更大幅度的香草酸受体1（TRPV1）样酸反应。辣椒素诱导的细胞内Ca~（2+）的增加在IB_4~+神经元中也稍大，在这些细胞中，其幅度与TRPV_1的免疫反应性水平相关，我们的数据表明，酸敏感离子通道（ASIC）和TRPV_1是小IB_4~+神经元中主要的酸敏感受体，而TRPV_1是IB_4~+神经元中的主要受体。由于ASIC样反应比TRPV1样反应对H+的变化敏感约10倍，我们推测小的IB4-而不是IB4+神经元在感知酸中起着重要作用。我们的研究结果还突出了IB4+和IB4-小神经元之间辣椒素反应的差异，并揭示了辣椒素反应和TRPV1表达水平之间的密切联系。(C)2004年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Protons play a key role in nociception caused by inflammation and ischaemia, but little is known about the relative sensitivities of different dorsal root ganglion (DRG) neurons. We have therefore examined the responses in vitro of rat DRG cells classified according to whether or not they bind Griffonia simplicifolia IB4 (IB4), a lectin which is widely used to distinguish between two major populations of small diameter neurons. Under voltage-clamp conditions, proton-activated inward currents were found in approximately 90% of small DRG neurons and showed one of three waveforms: transient, sustained or mixed. The majority of IB4-positive (IB4+) neurons (63%) gave rise to sustained inward currents that were sensitive to capsazepine. In contrast, the most prevalent waveform in small IB4-negative (IB4-) neurons (69%) was a mixed response containing transient and sustained components. The transient component was inhibited by amiloride whilst the sustained component showed a variable sensitivity to capsazepine. We also found that more IB4+ cells responded to capsaicin and, on average, gave rise to a larger magnitude of response than small IB4- neurons, consistent with their higher prevalence and greater amplitude of vanilloid receptor 1 (TRPV1)-like acid responses. The increase in intracellular Ca2+ induced by capsaicin was also slightly greater in IB4+ neurons and in these cells its magnitude correlated with the level of TRPV1 immunoreactivity.Our data suggest that acid-sensing ion channels (ASICs) and TRPV1 are the major acid-sensitive receptors in small IB4- neurons, whilst TRPV1 is the predominant one in IB4+ neurons. Because ASIC-like responses were approximately 10-fold more sensitive to changes in H+ than TRPV1-like responses, we speculate that small IB4- rather than IB4+ neurons play an essential role in sensing acid. Our results also highlight differences in capsaicin responses between IB4+ and IB4- small neurons and reveal the close link between capsaicin responses and levels of TRPV1 expression. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved.