Schmidt Manuela, Dubin Adrienne E, Petrus Matt J, Earley Taryn J, Patapoutian Ardem
Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Neuron. 2009 Nov 25;64(4):498-509. doi: 10.1016/j.neuron.2009.09.030.
Transient receptor potential A1 (TRPA1) ion channel senses a variety of noxious stimuli and is involved in nociception. Many TRPA1 agonists covalently modify the channel, which can lead to desensitization. The fate of modified TRPA1 and the mechanism of preserving its response to subsequent stimuli are not understood. Moreover, inflammatory signals sensitize TRPA1 by involving protein kinase A (PKA) and phospholipase C (PLC) through unknown means. We show that TRPA1-mediated nocifensive behavior can be sensitized in vivo via PKA/PLC signaling and by activating TRPA1 with the ligand mustard oil (MO). Interestingly, both stimuli increased TRPA1 membrane levels in vitro. Tetanus toxin attenuated the response to the second of two pulses of MO in neurons, suggesting that vesicle fusion increases functional surface TRPA1. Capacitance recordings suggest that MO can induce exocytosis. We propose that TRPA1 translocation to the membrane might represent one of the mechanisms controlling TRPA1 functionality upon acute activation or inflammatory signals.
瞬时受体电位A1（TRPA1）离子通道可感知多种有害刺激，并参与痛觉感受。许多TRPA1激动剂会与该通道发生共价修饰，这可能导致脱敏。修饰后的TRPA1的命运以及保留其对后续刺激反应的机制尚不清楚。此外，炎症信号通过未知方式涉及蛋白激酶A（PKA）和磷脂酶C（PLC）使TRPA1敏感化。我们发现，TRPA1介导的伤害防御行为在体内可通过PKA/PLC信号传导以及用配体芥子油（MO）激活TRPA1而敏感化。有趣的是，这两种刺激在体外均增加了TRPA1的膜水平。破伤风毒素减弱了神经元对两个MO脉冲中第二个脉冲的反应，表明囊泡融合增加了功能性表面TRPA1。电容记录表明MO可诱导胞吐作用。我们提出，TRPA1易位至膜可能代表了在急性激活或炎症信号作用下控制TRPA1功能的机制之一。
