Thermal TAP channels are important for thermal sensation and nociception, but their gating mechanisms have remained elusive. With optically generated submillisecond temperature steps from 22 degrees C to >60 degrees 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.
机构:
Harvard Univ, Childrens Hosp Boston, Sch Med,Dept Neurobiol, Howard Hughes Med Inst, Boston, MA 02115 USAHarvard Univ, Childrens Hosp Boston, Sch Med,Dept Neurobiol, Howard Hughes Med Inst, Boston, MA 02115 USA
机构:
Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USAScripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA
Grandl, Joerg
;
Hu, Hongzhen
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机构:
Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USAScripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA
Hu, Hongzhen
;
Bandell, Michael
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机构:Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA
Bandell, Michael
;
Bursulaya, Badry
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机构:Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA
Bursulaya, Badry
;
Schmidt, Manuela
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Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USAScripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA
Schmidt, Manuela
;
Petrus, Matt
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机构:
Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USAScripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA
Petrus, Matt
;
Patapoutian, Ardem
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机构:
Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA
Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USAScripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA
机构:
Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USAScripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA
Grandl, Joerg
;
Kim, Sung Eun
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机构:
Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USAScripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA
Kim, Sung Eun
;
Uzzell, Valerie
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Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USAScripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA
Uzzell, Valerie
;
Bursulaya, Badry
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Novartis Res Fdn, Genom Inst, San Diego, CA USAScripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA
Bursulaya, Badry
;
Petrus, Matt
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h-index: 0
机构:
Novartis Res Fdn, Genom Inst, San Diego, CA USAScripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA
Petrus, Matt
;
Bandell, Michael
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h-index: 0
机构:
Novartis Res Fdn, Genom Inst, San Diego, CA USAScripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA
Bandell, Michael
;
Patapoutian, Ardem
论文数: 0引用数: 0
h-index: 0
机构:
Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA
Novartis Res Fdn, Genom Inst, San Diego, CA USAScripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA
机构:
Harvard Univ, Childrens Hosp Boston, Sch Med,Dept Neurobiol, Howard Hughes Med Inst, Boston, MA 02115 USAHarvard Univ, Childrens Hosp Boston, Sch Med,Dept Neurobiol, Howard Hughes Med Inst, Boston, MA 02115 USA
机构:
Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USAScripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA
Grandl, Joerg
;
Hu, Hongzhen
论文数: 0引用数: 0
h-index: 0
机构:
Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USAScripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA
Hu, Hongzhen
;
Bandell, Michael
论文数: 0引用数: 0
h-index: 0
机构:Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA
Bandell, Michael
;
Bursulaya, Badry
论文数: 0引用数: 0
h-index: 0
机构:Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA
Bursulaya, Badry
;
Schmidt, Manuela
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h-index: 0
机构:
Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USAScripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA
Schmidt, Manuela
;
Petrus, Matt
论文数: 0引用数: 0
h-index: 0
机构:
Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USAScripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA
Petrus, Matt
;
Patapoutian, Ardem
论文数: 0引用数: 0
h-index: 0
机构:
Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA
Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USAScripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA
机构:
Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USAScripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA
Grandl, Joerg
;
Kim, Sung Eun
论文数: 0引用数: 0
h-index: 0
机构:
Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USAScripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA
Kim, Sung Eun
;
Uzzell, Valerie
论文数: 0引用数: 0
h-index: 0
机构:
Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USAScripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA
Uzzell, Valerie
;
Bursulaya, Badry
论文数: 0引用数: 0
h-index: 0
机构:
Novartis Res Fdn, Genom Inst, San Diego, CA USAScripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA
Bursulaya, Badry
;
Petrus, Matt
论文数: 0引用数: 0
h-index: 0
机构:
Novartis Res Fdn, Genom Inst, San Diego, CA USAScripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA
Petrus, Matt
;
Bandell, Michael
论文数: 0引用数: 0
h-index: 0
机构:
Novartis Res Fdn, Genom Inst, San Diego, CA USAScripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA
Bandell, Michael
;
Patapoutian, Ardem
论文数: 0引用数: 0
h-index: 0
机构:
Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA
Novartis Res Fdn, Genom Inst, San Diego, CA USAScripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA