The putative role of vanilloid receptor-like protein-1 in mediating high threshold noxious heat-sensitivity in rat cultured primary sensory neurons
The putative role of vanilloid receptor-like protein-1 in mediating high threshold noxious heat-sensitivity in rat cultured primary sensory neurons
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DOI：
10.1046/j.1460-9568.2002.02231.x
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发表时间：
2002-10-01
影响因子：
3.4
通讯作者：
Nagy, I
中科院分区：
文献类型：
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作者：
Ahluwalia, J;Rang, H;Nagy, I
在培养的大鼠初级感觉神经元中研究了高阈值有害热激活电流和类香草醛受体样蛋白 1 表达，以找出导致高阈值有害热敏感性的分子。平均温度阈值和高阈值有害热激活电流的幅度分别为 51.6 +/- 0.13 摄氏度和 -2.0 +/- 0.1nA（保持电位为 -60 mV）。高阈值有害热激活电流的电流-电压关系在正膜电位下呈线性，而在负膜电位下表现出弱的内向整流。在对照细胞内和细胞外溶液中测得的平均反转电位为 4.5 +/- 0.9 mV (n = 6)。离子取代表明，高阈值有害热激活电流是非选择性阳离子电流，计算出的离子渗透率为 Cs+ : Na+ : Ca2+ (1 : 1.3 : 4.5)。连续刺激将热阈值从 52.2 +/- 1 降低到 48.4 +/- 1.4 摄氏度，然后降低到 44 +/- 0.7 摄氏度 (n = 3)。钌红 (100 nM-10 muM) 可以剂量依赖性且可逆地降低高阈值有害热激活电流，但辣椒西平 (10 mM) 则不能。高阈值有害热敏感神经元的平均最长直径为 31.48 +/- 0.5 mum（A = 大约 778 mum(2)；n = 77）。总神经元群体的 23% 表达香草素受体样蛋白 1。类香草醛受体样蛋白1免疫阳性细胞的平均面积为1696 +/- 65.3 mum(2)（d = 与46 mum相似）。表达香草素受体样蛋白 1 的神经元不表达香草素受体 1。将我们的数据与表达香草素受体样蛋白 1 的非神经元细胞中获得的结果以及之前的免疫组织化学结果进行比较，表明高阈值有害热激活电流是由香草素受体样蛋白 1 产生的，并且高阈值热敏背根神经节神经元是 I 型有害热敏纤维的核周。
High threshold noxious heat-activated currents and vanilloid receptor-like protein-1 expression were studied in rat cultured primary sensory neurons to find out the molecule(s) responsible for high threshold noxious heat-sensitivity. The average temperature threshold and amplitude of high threshold noxious heat-activated currents were 51.6 +/- 0.13 degreesC and -2.0 +/- 0.1nA (at a holding potential of -60 mV), respectively. The current-voltage relationship of high threshold noxious heat-activated currents was linear at positive membrane potentials, while it showed a weak inward rectification at negative membrane potentials. The average reversal potential measured in control intracellular and extracellular solutions was 4.5 +/- 0.9 mV (n = 6). Ionic substitutions revealed that the high threshold noxious heat-activated current is a nonselective cationic current with calculated ionic permeabilities of Cs+ : Na+ : Ca2+ (1 : 1.3 : 4.5). Consecutive stimuli reduced the heat threshold from 52.2 +/- 1 to 48.4 +/- 1.4 degreesC and then to 44 +/- 0.7 degreesC (n = 3). High threshold noxious heat-activated currents could dose-dependently and reversibly be reduced by ruthenium red (100 nM-10 muM) but not by capsazepine (10 mM). The average longest diameter of high threshold noxious heat-sensitive neurons was 31.48 +/- 0.5 mum (A = approximate to778 mum(2); n = 77). Twenty-three percent of the total neuronal population expressed vanilloid receptor-like protein-1. The average area of the vanilloid receptor-like protein-1-immunopositive cells was 1696 +/- 65.3 mum(2) (d = similar to46 mum). Vanilloid receptor-like protein-1-expressing neurons did not express the vanilloid receptor 1. Comparison of our data with results obtained in vanilloid receptor-like protein-1-expressing non-neuronal cells and previous immunohistochemical findings suggests that high threshold noxious heat-activated currents are produced by vanilloid receptor-like protein-1 and that high threshold heat-sensitive dorsal root ganglion neurons are the perikarya of type I noxious heat-sensitive fibers.