Pore region of TRPV3 ion channel is specifically required for heat activation

Jörg Grandl, Hongzhen Hu, Michael Bandell, Badry Bursulaya, Manuela Schmidt, Matt Petrus, Ardem Patapoutian

Research output: Contribution to journalArticlepeer-review

129 Scopus citations

Abstract

Ion channels can be activated (gated) by a variety of stimuli, including chemicals, voltage, mechanical force or temperature. Although molecular mechanisms of ion channel gating by chemical and voltage stimuli are understood in principal, the mechanisms of temperature activation remain unknown. The transient receptor potential channel TRPV3 is a nonselective cation channel that is activated by warm temperatures and sensory chemicals such as camphor. Here we screened ∼14,000 random mutant clones of mouse TRPV3 and identified five single point mutations that specifically abolish heat activation but do not perturb chemical activation or voltage modulation. Notably, all five mutations are located in the putative sixth transmembrane helix and the adjacent extracellular loop in the pore region of mouse TRPV3. Although distinct in sequence, we found that the corresponding loop of frog TRPV3 is also specifically required for heat activation. These findings demonstrate that the temperature sensitivity of TRPV3 is separable from all other known activation mechanisms and implicate a specific region in temperature sensing.

Original languageEnglish
Pages (from-to)1007-1013
Number of pages7
JournalNature neuroscience
Volume11
Issue number9
DOIs
StatePublished - Sep 2008

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