Overview
- UCSF researchers report the first molecular movie of TRPM8, the ion channel that lets nerves detect cold and menthol, in a paper published in Nature.
- As temperature drops below about 26°C, a key pillar inside the protein straightens and lifts like a latch, which opens the pore and starts a cold signal to the brain.
- The team kept the channel in native-like membranes using high‑frequency ultrasound extraction, then combined cryo‑electron microscopy with hydrogen–deuterium exchange mass spectrometry to see both snapshots and motion.
- A cross‑species test found mammalian TRPM8 is highly dynamic and cold‑sensitive, while the bird version holds a steadier shape and is mostly cold‑insensitive.
- The mechanism could guide selective blockers for conditions like cold allodynia, and the group plans to map how TRPM8 inhibitors now in pain trials change the channel’s shape.