In principle, the same temperature-control mechanism is prevalent in all types of bistable channels, as well as other functional membrane proteins. However, their
T½ values do not necessarily appear in a range that is physiologically relevant. In these cases, the energy term −
TΔ
S is combined with other energy terms inside Δ
GC. For example, −
TΔ
S is usually incorporated into the
V½Q term of the voltage-gating channel without explicit discussion. In contrast, when thermo-gating mechanisms are considered for a given channel,
VQ is commonly incorporated into the
T½Δ
S term, in order to highlight temperature variation as the dominant gating factor. In a more complex model, it is feasible to construct a joint opening probability equation for polymodal bistate channels that simultaneously implement thermo-, voltage-, ligand binding-, and membrane tension-gating mechanisms (Zhang
2021). Within a unified thermodynamic framework, the bistable-model hypothesis discussed above provides a satisfactory simplification for the thermo-gating mechanism, as long as the transition with the steepest temperature dependence is rate limiting. The existence of such a mechanism warrants further investigation, either to be verified or falsified experimentally. Such experiments may include thermo-denaturation and mutagenesis studies on channel properties, among others. Until then, we propose that our model serves as the best possible explanation for the temperature-sensing mechanism of thermo-gating channels.