Xing Jihong, Li Jianhua
Heart and Vascular Institute and Department of Medicine, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033, USA.
J Neurophysiol. 2007 Jan;97(1):503-11. doi: 10.1152/jn.01023.2006. Epub 2006 Oct 25.
The purpose of this study was to determine the role of transient receptor potential vanilloid type 1 (TRPV1) receptor in modulating neuronal activity of the dorsolateral periaqueductal gray (dl-PAG) through excitatory and inhibitory synaptic inputs. First, whole cell voltage-clamp recording was performed to obtain the spontaneous miniature excitatory postsynaptic currents (mEPSCs) and inhibitory postsynaptic currents (mIPSCs) of the dl-PAG neurons. As 1 microM of capsaicin was applied into the perfusion chamber, the frequency of mEPSCs was increased from 3.21 +/- 0.49 to 5.64 +/- 0.64 Hz (P < 0.05, n = 12) without altering the amplitude and the decay time constant of mEPSCs. In contrast, capsaicin had no distinct effect on mIPSCs. A specific TRPV1 receptor antagonist, iodo-resiniferatoxin (i-RTX, 300 nM), decreased the frequency of mEPSCs from 3.51 +/- 0.29 to 2.01 +/- 0.2 Hz (P < 0.05, n = 8) but did not alter the amplitude and decay time. In addition, i-RTX applied into the chamber abolished the effect of capsaicin on mEPSC of the dl-PAG. In another experiment, spontaneous action potential of the dl-PAG neurons was recorded using whole cell current-clamp methods. Capsaicin significantly elevated the discharge rate of the dl-PAG neurons from 3.03 +/- 0.38 to 5.96 +/- 0.87 Hz (n = 8). The increased firing activity was abolished in the presence of glutamate N-methy-D-aspartate (NMDA) and non-NMDA antagonists, 2-amino-5-phosphonopentanoic acid, and 6-cyano-7-nitroquinoxaline-2,3-dione. The results from this study provide the first evidence indicating that activation of TRPV1 receptors increases the neuronal activity of the dl-PAG through selective potentiation of glutamatergic synaptic inputs.
本研究的目的是确定瞬时受体电位香草酸亚型1（TRPV1）受体通过兴奋性和抑制性突触输入调节背外侧导水管周围灰质（dl-PAG）神经元活动中的作用。首先，进行全细胞电压钳记录以获得dl-PAG神经元的自发性微小兴奋性突触后电流（mEPSCs）和抑制性突触后电流（mIPSCs）。当向灌流槽中加入1微摩尔辣椒素时，mEPSCs的频率从3.21±0.49赫兹增加到5.64±0.64赫兹（P<0.05，n = 12），而mEPSCs的幅度和衰减时间常数未改变。相比之下，辣椒素对mIPSCs没有明显影响。一种特异性TRPV1受体拮抗剂，碘树脂毒素（i-RTX，300纳摩尔），使mEPSCs的频率从3.51±0.29赫兹降低到2.01±0.2赫兹（P<0.05，n = 8），但未改变其幅度和衰减时间。此外，向槽中加入i-RTX消除了辣椒素对dl-PAG的mEPSC的作用。在另一项实验中，使用全细胞电流钳方法记录dl-PAG神经元的自发性动作电位。辣椒素使dl-PAG神经元的放电频率从3.03±0.38赫兹显著提高到5.96±0.87赫兹（n = 8）。在存在谷氨酸N-甲基-D-天冬氨酸（NMDA）和非NMDA拮抗剂2-氨基-5-磷酸戊酸及6-氰基-7-硝基喹喔啉-2,3-二酮的情况下，增加的放电活动被消除。本研究结果提供了首个证据，表明TRPV1受体的激活通过选择性增强谷氨酸能突触输入来增加dl-PAG的神经元活动。
