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Biophys J. 2010 Sep 22;99(6):1743-53. doi: 10.1016/j.bpj.2010.07.022.

Kinetic and energetic analysis of thermally activated TRPV1 channels.

Author information

1
Department of Physiology and Biophysical Sciences, State University of New York, Buffalo, New York, USA.

Abstract

Thermal TRP channels are important for thermal sensation and nociception, but their gating mechanisms have remained elusive. With optically generated submillisecond temperature steps from 22°C to >60°C, we have directly measured the activation and deactivation kinetics of TRPV1 channels, and from the measurements we determined the energetics of thermal gating. We show that activation by temperature follows single exponential time courses. It occurs in a few milliseconds and is significantly faster than activation by agonists. The gating has characteristics of a melting process involving large compensatory enthalpy (>100 kcal/mol) and entropy changes with little free energy change. The reaction path is asymmetrical with temperature mainly driving the opening while the closing has nominal but negative temperature dependence (i.e., sensitivity to cold). Both voltage and agonists alter the slope of the temperature-dependent gating curve as well as shifting the midpoint. However, compared to the energetic effect of temperature on gating, the effect of voltage is small. Our data on the interdependence between voltage and direct temperature responses are not fit to a model involving independent stimuli but instead support a temperature-sensing mechanism that is coupled to charge movement or agonist binding.

PMID:
20858418
PMCID:
PMC2941006
DOI:
10.1016/j.bpj.2010.07.022
[Indexed for MEDLINE]
Free PMC Article

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