Ni Dan, Lee Lu-Yuan
Department of Physiology, University of Kentucky Medical Center, Lexington, KY 40536-0298, USA.
Am J Physiol Lung Cell Mol Physiol. 2008 Mar;294(3):L563-71. doi: 10.1152/ajplung.00336.2007. Epub 2008 Jan 4.
Hyperthermia has been shown to sensitize vagal pulmonary C-fibers in anesthetized rats. However, it was not clear whether the effect was due to a direct action of hyperthermia on these sensory neurons. To answer this question, we carried out this study to determine the effect of increasing temperature on the responses to various chemical stimuli in isolated nodose and jugular ganglion neurons innervating the rat lungs. In the whole cell perforated patch-clamp study, when the temperature was increased from normal (approximately 36 degrees C) to hyperthermic (approximately 40.6 degrees C) level of the rat body temperature, the inward currents evoked by capsaicin, a selective activator of the transient receptor potential vanilloid type 1 (TRPV1), and 2-aminoethoxydiphenyl borate (2-APB), a nonselective activator of TRPV1-3 receptors, were both significantly increased. This potentiating effect was clearly present even at a moderate level of hyperthermia (approximately 39 degrees C). However, only the slow, sustained component of acid-evoked current mediated through the TRPV1 receptor was potentiated by hyperthermia, whereas the rapid, transient component was inhibited. In contrast, the currents evoked by adenosine 5'-triphosphate and acetylcholine, neither of which is known to activate the TRPV1 channel, did not increase when the same temperature elevation was applied. Furthermore, the hyperthermia-induced potentiation of the cell response to 2-APB was significantly attenuated by either capsazepine or AMG 9810, selective TRPV1 antagonists. In conclusion, increasing temperature within the physiological range exerts a potentiating effect on the response to TRPV1 activators in these neurons, which is probably mediated through a positive interaction between hyperthermia and these chemical activators at the TRPV1 channel.
高温已被证明能使麻醉大鼠的迷走神经肺C纤维敏感化。然而，尚不清楚这种效应是否是由于高温对这些感觉神经元的直接作用。为了回答这个问题，我们开展了本研究，以确定温度升高对支配大鼠肺的孤立结节和颈静脉神经节神经元对各种化学刺激反应的影响。在全细胞穿孔膜片钳研究中，当温度从大鼠正常体温（约36℃）升高到高温（约40.6℃）水平时，辣椒素（一种瞬时受体电位香草酸亚型1（TRPV1）的选择性激活剂）和2-氨基乙氧基二苯硼酸（2-APB，一种TRPV1-3受体的非选择性激活剂）诱发的内向电流均显著增加。即使在中度高温（约39℃）水平，这种增强效应也明显存在。然而，高温仅增强了通过TRPV1受体介导的酸诱发电流的缓慢、持续成分，而快速、瞬时成分则受到抑制。相比之下，当施加相同的温度升高时，由三磷酸腺苷和乙酰胆碱诱发的电流（已知两者均不激活TRPV1通道）并未增加。此外，辣椒平或AMG 9810（选择性TRPV1拮抗剂）可显著减弱高温诱导的细胞对2-APB反应的增强作用。总之，在生理范围内升高温度对这些神经元对TRPV1激活剂的反应具有增强作用，这可能是通过高温与这些化学激活剂在TRPV1通道上的正向相互作用介导的。
