Thermodynamics of Heat Activation of Single Capsaicin Ion Channels VR1

AbstractTemperature affects functions of all ion channels, but few of them can be gated directly. The vanilloid receptor VR1 provides one exception. As a pain receptor, it is activated by heat >42°C in addition to other noxious stimuli, e.g. acids and vanilloids. Although it is understood how ligand- and voltage-gated channels might detect their stimuli, little is known on how heat could be sensed and activate a channel. In this study, we characterized the heat-induced single-channel activity of VR1, in an attempt to localize the temperature-dependent components involved in the activation of the channel. At <42°C, openings were few and brief. Raising the ambient temperature rapidly increased the frequency of openings. Despite the large temperature coefficient of the apparent activity (Q10 ≈ 27), the unitary current, the open dwell-times, and the intraburst closures were all only weakly temperature dependent (Q10