Journal Article

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

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

2008

Overview

Although certain ion channels can be gated by temperature, it is currently unknown how this occurs. Here, the authors identify regions of TRPV3 that are critical for heat sensation, yet independent of other channel gating mechanisms. 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.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: Animal Genetics and Genomics / Animals / Anura / Behavioral Sciences / Biological Techniques / Biomedical and Life Sciences / Biomedicine / Biophysics / Boron Compounds - pharmacology / Cell Line, Transformed / Cloning / Cloning, Molecular / Electric Stimulation / Heat / Hot Temperature / Humans / Ion Channel Gating - drug effects / Ion Channel Gating - genetics / Ion Channel Gating - physiology / Ion channels / Membrane Potentials - drug effects / Membrane Potentials - genetics / Membrane Potentials - physiology / Models, Molecular / Mutation / Mutation - physiology / Neurobiology / Neurogenetics / Neurosciences / Patch-Clamp Techniques / Physiological aspects / Physiology / Sensory receptors / Temperature / Transfection - methods / TRPV Cation Channels - chemistry / TRPV Cation Channels - genetics / TRPV Cation Channels - physiology / Xenopus - genetics