The detection of mechanical touch and temperature is essential for interaction with the physical world. Here, we report that cold potentiates the conversion of mechanical touch into excitatory ionic current in cutaneous mechanoreceptors from different vertebrate species. We show that this process is mediated by the mechanically gated ion channel Piezo2, the principal detector of touch in somatosensory neurons, and can be recapitulated by Piezo2 orthologs in various heterologous systems. We demonstrate that the blade domains are essential for cold-induced potentiation of Piezo2 activity and are sufficient to endow this property when transposed onto Piezo2 homolog Piezo1. Our findings provide mechanistic insights into thermal–tactile interaction in vertebrates at the level of somatosensory neurons.
Tactile information is detected by thermoreceptors and mechanoreceptors in the skin and integrated by the central nervous system to produce the perception of somatosensation. Here we investigate the mechanism by which thermal and mechanical stimuli begin to interact and report that it is achieved by the mechanotransduction apparatus in cutaneous mechanoreceptors. We show that moderate cold potentiates the conversion of mechanical force into excitatory current in all types of mechanoreceptors from mice and tactile-specialist birds. This effect is observed at the level of mechanosensitive Piezo2 channels and can be replicated in heterologous systems using Piezo2 orthologs from different species. The cold sensitivity of Piezo2 is dependent on its blade domains, which render the channel resistant to cold-induced perturbations of the physical properties of the plasma membrane and give rise to a different mechanism of mechanical activation than that of Piezo1. Our data reveal that Piezo2 is an evolutionarily conserved mediator of thermal–tactile integration in cutaneous mechanoreceptors.