TRP Channel Thermal Dynamics

Science's STKE  17 Aug 2004:
Vol. 2004, Issue 246, pp. tw292
DOI: 10.1126/stke.2462004tw292

The relief you feel on walking into an air-conditioned building on a sweltering summer day is accompanied by a switch in the particular set of temperature-sensitive transient receptor potential (TRP) channels active in your sensory neurons. Voets et al. used patch-clamp analysis of channels transiently expressed in human embryonic kidney (HEK) 293 cells to investigate the mechanisms that underlie gating of TRPM8, which is activated by cold, and TRPV1, which is activated by heat. Both TRPM8 and TRPV1 were activated by membrane depolarization. Cooling TRPM8 or heating TRPV1 elicited graded shifts in the voltage dependence of activation so that the channels opened in response to more moderate depolarizations. The midpoint voltage (V1/2) for TRPM8 activation was about +200 mV at 37°C and about +25 mV at 5 to 10°C; V1/2 for TRPV1 was around 150 mV at 15°C and around –50 mV at 40 to 45°C. Agonists (menthol for TRPM8 and capsaicin for TRPV1) also shifted the voltage dependence of activation to lower voltages. Kinetic analysis of voltage-dependent channel opening and closing indicated that the rate of TRPM8 opening was only slightly temperature dependent, whereas the rate of TRPM8 closing was highly temperature dependent, with an activation energy approximately 10 times as high as that for opening. In contrast, the opening rate of TRPV1 was steeply temperature dependent, whereas the closing rate was not. Thus, the authors propose that temperature sensitivity of both cold-sensitive and heat-sensitive TRP channels is linked to their voltage-dependent gating and depends on differences in the activation energies of voltage-dependent channel opening and closing.

T. Voets, G. Droogman, U. Wissenbach, A. Janssens, V. Flockerzi, B. Nilius, The principle of temperature-dependent gating in cold- and heat-sensitive TRP channels. Nature 430, 748-754 (2004). [Online Journal]