Gachon Pain Center and Department of Physiology, College of Medicine, Gachon University, Incheon 21999, Korea.
Department of Neurosurgery, Spine tumor center, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea.
Int J Mol Sci. 2020 May 28;21(11):3834. doi: 10.3390/ijms21113834.
Piezo channels are mechanosensitive ion channels. Piezo1 is primarily expressed in nonsensory tissues, whereas Piezo2 is predominantly found in sensory tissues, including dorsal root ganglion (DRG) neurons. However, a recent study demonstrated the intracellular calcium response to Yoda1, a selective Piezo1 agonist, in trigeminal ganglion (TG) neurons. Herein, we investigate the expression of mRNA and protein in mouse and human DRG neurons and the activation of Piezo1 via calcium influx by Yoda1. Yoda1 induces inward currents mainly in small- (< 25 μm) and medium-sized (25-35 μm) mouse DRG neurons. The Yoda1-induced Ca response is inhibited by cationic channel blocker, ruthenium red and cationic mechanosensitive channel blocker, GsMTx4. To confirm the specific inhibition of Piezo1, we performed an adeno-associated virus serotype 2/5 (AAV2/5)-mediated delivery of short hairpin RNA (shRNA) into mouse DRG neurons. AAV2/5 transfection downregulates mRNA expression and reduces Ca response by Yoda1. Piezo1 also shows physiological functions with transient receptor potential vanilloid 1 (TRPV1) in the same DRG neurons and is regulated by the activation of TRPV1 in mouse DRG sensory neurons. Overall, we found that Piezo1 has physiological functions in DRG neurons and that TRPV1 activation inhibits an inward current induced by Yoda1.
Piezo 通道是机械敏感的离子通道。Piezo1 主要在非感觉组织中表达，而 Piezo2 主要在感觉组织中表达，包括背根神经节 (DRG) 神经元。然而，最近的一项研究表明，Yoda1（一种选择性的 Piezo1 激动剂）可引起三叉神经节 (TG) 神经元的细胞内钙反应。在此，我们研究了 Piezo1 在小鼠和人 DRG 神经元中的 mRNA 和蛋白表达情况，以及 Yoda1 通过钙内流激活 Piezo1 的情况。Yoda1 主要在小 (<25 μm) 和中 (25-35 μm) 型小鼠 DRG 神经元中诱导内向电流。Yoda1 诱导的 Ca 反应被阳离子通道阻断剂钌红和阳离子机械敏感通道阻断剂 GsMTx4 抑制。为了确认 Piezo1 的特异性抑制，我们用腺相关病毒血清型 2/5 (AAV2/5) 将短发夹 RNA (shRNA) 转染到小鼠 DRG 神经元中。AAV2/5 转染下调 Piezo1 的 mRNA 表达，并降低 Yoda1 诱导的 Ca 反应。Piezo1 还与同一 DRG 神经元中的瞬时受体电位香草酸 1 (TRPV1) 具有生理功能，并受 TRPV1 在小鼠 DRG 感觉神经元中的激活调节。总的来说，我们发现 Piezo1 在 DRG 神经元中具有生理功能，并且 TRPV1 的激活抑制了 Yoda1 诱导的内向电流。
