The Role of Allosteric Coupling on Thermal Activation of Thermo-TRP Channels

Thermo-transient receptor potential channels display outstanding temperature sensitivity and can be directly gated by low or high temperature, giving rise to cold-and heat-activated currents. These constitute the molecular basis for the detection of changes in ambient temperature by sensory neurons in animals. The mechanism that underlies the temperature sensitivity in thermo-transient receptor potential channels remains unknown, but has been associated with large changes in standard-state enthalpy (Delta H degrees) and entropy (Delta S degrees) upon channel gating. The magnitude, sign, and temperature dependence of Delta H degrees and Delta S degrees, the last given by an associated change in heat capacity (Delta C-p), can determine a channel's temperature sensitivity and whether it is activated by cooling, heating, or both, if Delta C-p makes an important contribution. We show that in the presence of allosteric gating, other parameters, besides Delta H degrees and Delta S degrees, including the gating equilibrium constant, the strength- and temperature dependence of the coupling between gating and the temperature-sensitive transitions, as well as the Delta H degrees/Delta S degrees ratio associated with them, can also determine a channel's temperature-dependent activity, and even give rise to channels that respond to both cooling and heating in a Delta C-p-independent manner.