哺乳动物对温度的感觉靠的是属于TRP离子通道家族的传感器。这些通道响应于热或冷刺激而出现的开启,会导致专门神经细胞(例如皮肤或嘴里的神经细胞)被激发,后者将热量信息传递给脊索和大脑。TRP通道响应温度变化所发生的激发的基本原理仍然基本上不为人们所知。Voets等人现在发现,在一种冷传感器TPM8和一种热传感器TRPV1中,温度传感靠的是一个机制。两个通道都显示出温度灵敏度非常高的电压门控,说明电压与温度传感之间有一个我们未曾料到的联系。这一将冷热传感统一起来的发现加深了我们对温度传感的了解,并且可能有助于我们了解与感觉紊乱症状(如冷超敏(即对冷过于敏感)或炎症)相关的病理条件。
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. (Thomas.Voets@med.kuleuven.ac.be).
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.