Pore turret of thermal TRP channels is not essential for temperature sensing

Abstract

Temperature-gated transient receptor potential (TRP) channels are the key players in thermal sensation. Temperature gating is made possible by relatively small free energy changes with large compensating changes in enthalpy and entropy. However, the structural changes that are correlated with the energy changes are not known (1–3). Recently, Yang et al. (4) concluded that the pore turret of thermal TRP channels is “part of the temperature-sensing apparatus.” They replaced a 14-residue region of the turret of TRPV1 (613–626) with a glycine-based fragment of equal length and found that it inhibited the thermal response. We question this interpretation. We previously studied the same region in TRPV1 (one residue longer, T612–S626) and found that it is functionally redundant (5). In particular, TRPV3, a homologous heat-activated channel, does not contain the region studied by Yang et al. (4). Furthermore, after we deleted the region T612–S626 in TRPV1, it did not lose temperature sensitivity (Fig. 1) or capsaicin and low pH responses (5). The contradiction between our data and those of Yang et al. has occurred perhaps because the substitution by Yang et al. (5) exerted an unintended effect on channel structure.