Parameters of Piezo2 channels.

Merkel cells combine with Aβ afferents, producing slowly adapting type 1(SA1) responses to mechanical stimuli. However, how Merkel cells transduce mechanical stimuli into neural signals to Aβ afferents is still unclear. Here we develop a biophysical model of Merkel cells for mechanical transduction by incorporating main ingredients such as Ca2+ and K+ voltage-gated channels, Piezo2 channels, internal Ca2+ stores, neurotransmitters release, and cell deformation. We first validate our model with several experiments. Then we reveal that Ca2+ and K+ channels on the plasma membrane shape the depolarization of membrane potentials, further regulating the Ca2+ transients in the cells. We also show that Ca2+ channels on the plasma membrane mainly inspire the Ca2+ transients, while internal Ca2+ stores mainly maintain the Ca2+ transients. Moreover, we show that though Piezo2 channels are rapidly adapting mechanical-sensitive channels, they are sufficient to inspire sustained Ca2+ transients in Merkel cells, which further induce the release of neurotransmitters for tens of seconds. Thus our work provides a model that captures the membrane potentials and Ca2+ transients features of Merkel cells and partly explains how Merkel cells transduce the mechanical stimuli by Piezo2 channels.

默克尔细胞与Aβ传入神经纤维结合后，可对机械刺激产生慢适应1型（slowly adapting type 1, SA1）响应。然而，默克尔细胞如何将机械刺激转换为神经信号并传递给Aβ传入神经纤维，目前仍未明确。本研究构建了用于机械转导（mechanical transduction）的默克尔细胞生物物理模型，整合了钙离子（Ca2+）与钾离子（K+）电压门控通道、Piezo2通道、细胞内钙库、神经递质释放及细胞形变等核心组分。我们首先通过多项实验对该模型进行了验证。随后的研究结果表明，细胞膜上的钙通道与钾通道可塑造膜电位的去极化过程，进而调控细胞内的钙瞬变（Ca2+ transients）。我们还发现，细胞膜上的钙通道主要触发钙瞬变的产生，而细胞内钙库则主要维持钙瞬变的持续存在。此外，尽管Piezo2通道属于快速适应型机械敏感通道，但其足以触发默克尔细胞内的持续性钙瞬变，进而诱导神经递质长达数十秒的释放。综上，本研究构建的模型能够复现默克尔细胞的膜电位与钙瞬变特征，并部分解释了默克尔细胞通过Piezo2通道完成机械刺激转导的分子机制。