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. Author summary: Touch is an essential way for humans to sense the physical world. It is necessary to figure out how our tactile system works. However, how Merkel cells convey mechanical stimuli into neural signals and deliver them to Aβ afferents is still poorly understood. In this work, we develop a biophysical model of Merkel cells for mechanical transduction. We show that Ca2+ and K+ channels on the plasma membrane control the membrane potentials of Merkel cells and further regulate the Ca2+ transients in the cells. Ca2+ channels on ER and MT directly contribute to the Ca2+ transients. Under indentation, the influx of Ca2+ through Piezo2 channels is sufficient to trigger the Ca2+ transients in Merkel cells and internal Ca2+ stores inherit to maintain the Ca2+ transients, which further result in a sustained release of neurotransmitters that activates the Aβ afferents. Thus our findings partly explain how Merkel cells combine with Aβ afferents to generate an SA1 response to sustained indentation by Piezo2 channels. [ABSTRACT FROM AUTHOR]