Piezo2 channels are expressed in Merkel cells and somatosensory neurons to mediate mechanotransduction leading to the sense of touch. Cytoskeletons including microtubules are key intracellular structures that maintain cellular membrane mechanics and thereby may be important in mechanotransduction. In the present study, we have explored, with microtubule-targeting agents, the potential role of microtubules in Piezo2-mediated mechanotransduction in Merkel cells of mouse whisker hair follicles. Applying patch-clamp recordings to Merkel cells in situ in whisker hair follicles, we show that Piezo2-mediated mechanically activated (MA) currents in Merkel cells are significantly potentiated by microtubule stabilizer paclitaxel, but reduced by microtubule destabilizer vincristine. Furthermore, electrophysiological recordings made from whisker hair follicle afferent nerves show that mechanically evoked whisker afferent impulses are significantly enhanced by paclitaxel and its analog docetaxel, but significantly suppressed by vincristine and its analog vinblastine. Our findings suggest that microtubules play an essential role in Piezo2 mechanotransduction in Merkel cells.

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微管在小鼠默克尔细胞 Piezo2 机械转导中的作用

Piezo2 通道在默克尔细胞和体感神经元中表达，以介导导致触觉的机械转导。包括微管在内的细胞骨架是维持细胞膜力学的关键细胞内结构，因此在机械转导中可能很重要。在本研究中，我们使用微管靶向剂探索了微管在小鼠胡须毛囊默克尔细胞中 Piezo2 介导的机械转导中的潜在作用。将膜片钳记录应用于晶须毛囊中的原位默克尔细胞，我们表明默克尔细胞中 Piezo2 介导的机械激活 (MA) 电流被微管稳定剂紫杉醇显着增强，但被微管去稳定剂长春新碱降低。此外，从晶须毛囊传入神经获得的电生理记录表明，紫杉醇及其类似物多西紫杉醇显着增强了机械诱发的晶须传入冲动，但被长春新碱及其类似物长春碱显着抑制。我们的研究结果表明，微管在默克尔细胞中的 Piezo2 机械转导中起着至关重要的作用。