Thermodynamics of heat activation of single capsaicin ion channels VR1.
Temperature 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 degrees 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 degrees 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 (Q(10) approximately 27), the unitary current, the open dwell-times, and the intraburst closures were all only weakly temperature dependent (Q(10) < 2). Instead, heat had a localized effect on the reduction of long closures between bursts (Q(10) approximately 7) and the elongation of burst durations (Q(10) approximately 32). Both membrane lipids and solution ionic strength affected the temperature threshold of the activation, but neither diminished the response. The thermodynamic basis of heat activation is discussed, to elucidate what makes a thermal-sensitive channel unique.
Department of Physiology and Biophysical Sciences, State University of New York at Buffalo, Buffalo, New York 14214, USA.
Beiying
B
Liu
Kwokyin
K
Hui
Feng
F
Qin
D000818:Animals; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D003198:Computer Simulation; D006358:Hot Temperature; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology* / Q000528:radiation effects*; D007668:Kidney / Q000196:embryology / Q000502:physiology / Q000528:radiation effects; D008564:Membrane Potentials / Q000502:physiology* / Q000528:radiation effects*; D008954:Models, Biological; D009865:Oocytes / Q000502:physiology / Q000528:radiation effects; D051381:Rats; D011955:Receptors, Drug / Q000187:drug effects* / Q000502:physiology*; D013045:Species Specificity; D013816:Thermodynamics; D014982:Xenopus laevis
D011955:Receptors, Drug; D002784:Cholesterol