哺乳動(dòng)物對(duì)溫度的感覺(jué)靠的是屬于TRP離子通道家族的傳感器,。這些通道響應(yīng)于熱或冷刺激而出現(xiàn)的開(kāi)啟,會(huì)導(dǎo)致專(zhuān)門(mén)神經(jīng)細(xì)胞(例如皮膚或嘴里的神經(jīng)細(xì)胞)被激發(fā),,后者將熱量信息傳遞給脊索和大腦,。TRP通道響應(yīng)溫度變化所發(fā)生的激發(fā)的基本原理仍然基本上不為人們所知。Voets等人現(xiàn)在發(fā)現(xiàn),,在一種冷傳感器TPM8和一種熱傳感器TRPV1中,,溫度傳感靠的是一個(gè)機(jī)制。兩個(gè)通道都顯示出溫度靈敏度非常高的電壓門(mén)控,,說(shuō)明電壓與溫度傳感之間有一個(gè)我們未曾料到的聯(lián)系,。這一將冷熱傳感統(tǒng)一起來(lái)的發(fā)現(xiàn)加深了我們對(duì)溫度傳感的了解,并且可能有助于我們了解與感覺(jué)紊亂癥狀(如冷超敏(即對(duì)冷過(guò)于敏感)或炎癥)相關(guān)的病理?xiàng)l件,。
The principle of temperature-dependent gating in cold- and heat-sensitive TRP channels
THOMAS VOETS1, GUY DROOGMANS1, ULRICH WISSENBACH2, ANNELIES JANSSENS1, VEIT FLOCKERZI2 & BERND NILIUS1
1 Laboratory of Physiology, Campus Gasthuisberg, KU Leuven, B-3000 Leuven, Belgium
2 Experimentelle und Klinische Pharmakologie und Toxikologie, Medizinische Fakultät, Universität des Saarlandes, D-66421 Homburg, Germany
Correspondence and requests for materials should be addressed to T.V. ([email protected]).
The mammalian sensory system is capable of discriminating thermal stimuli ranging from noxious cold to noxious heat. Principal temperature sensors belong to the TRP cation channel family, but the mechanisms underlying the marked temperature sensitivity of opening and closing ('gating') of these channels are unknown. Here we show that temperature sensing is tightly linked to voltage-dependent gating in the cold-sensitive channel TRPM8 and the heat-sensitive channel TRPV1. Both channels are activated upon depolarization, and changes in temperature result in graded shifts of their voltage-dependent activation curves. The chemical agonists menthol (TRPM8) and capsaicin (TRPV1) function as gating modifiers, shifting activation curves towards physiological membrane potentials. Kinetic analysis of gating at different temperatures indicates that temperature sensitivity in TRPM8 and TRPV1 arises from a tenfold difference in the activation energies associated with voltage-dependent opening and closing. Our results suggest a simple unifying principle that explains both cold and heat sensitivity in TRP channels.