The study investigates the temperature-dependent gating mechanisms in cold-sensitive TRPM8 and heat-sensitive TRPV1 channels. Both channels are activated by membrane depolarization, and their voltage-dependent activation curves shift with temperature changes. Chemical agonists like menthol (for TRPM8) and capsaicin (for TRPV1) modify the activation curves by shifting them towards physiological membrane potentials. Kinetic analysis reveals that the temperature sensitivity in TRPM8 and TRPV1 arises from a tenfold difference in the activation energies associated with voltage-dependent opening and closing. This suggests a unifying principle where the difference in activation energies explains both cold and heat sensitivity in TRP channels. The findings indicate that temperature sensing in these channels is membrane-delimited and influenced by transmembrane voltage, challenging previous models that relied on temperature-dependent binding of second messengers or lipid membrane phase transitions. The study also explores the effects of ligand activators, showing that menthol and capsaicin can potentiate the thermal responses by modifying the voltage-dependent properties of the channels.The study investigates the temperature-dependent gating mechanisms in cold-sensitive TRPM8 and heat-sensitive TRPV1 channels. Both channels are activated by membrane depolarization, and their voltage-dependent activation curves shift with temperature changes. Chemical agonists like menthol (for TRPM8) and capsaicin (for TRPV1) modify the activation curves by shifting them towards physiological membrane potentials. Kinetic analysis reveals that the temperature sensitivity in TRPM8 and TRPV1 arises from a tenfold difference in the activation energies associated with voltage-dependent opening and closing. This suggests a unifying principle where the difference in activation energies explains both cold and heat sensitivity in TRP channels. The findings indicate that temperature sensing in these channels is membrane-delimited and influenced by transmembrane voltage, challenging previous models that relied on temperature-dependent binding of second messengers or lipid membrane phase transitions. The study also explores the effects of ligand activators, showing that menthol and capsaicin can potentiate the thermal responses by modifying the voltage-dependent properties of the channels.