Thermoring basis for thermo-gated TRPV2

Abstract The heat response of the homotetrameric thermosensitive transient receptor potential vanilloid 2 (TRPV2) channel is use-dependent. The initial short heat stimulus typically decreases the temperature threshold and sensitivity for the subsequent one. However, the precise structural basis for this use-dependence has not been well understood. In this study, the 3D cryo-EM structures of apo rat TRPV2 in different gating states at low temperatures were analyzed using a highly sensitive thermoring model. The results indicated that two pre-open closed states shared a common cold-evoked open state with matched thresholds and thermosensitivities to mirror the first and second heat sensations. Therefore, the heat capacity mechanism could also be applied to elucidate the unique thermoring basis for the use-dependent heat responses of thermosensitive TRPV2 channel. (122 words)