Dual amplification strategy turns TRPM2 channels into supersensitive central heat detectors.

ABSTRACT: The Ca²⁺ and ADP ribose (ADPR)-activated cation channel TRPM2 is the closest homolog of the cold sensor TRPM8 but serves as a deep-brain warmth sensor. To unravel the molecular mechanism of heat sensing by the TRPM2 protein, we study here temperature dependence of TRPM2 currents in cell-free membrane patches across ranges of agonist concentrations. We find that channel gating remains strictly agonist-dependent even at 40°C: heating alone or in combination with just Ca²⁺, just ADPR, Ca²⁺ + cyclic ADPR, or H₂O₂ pretreatment only marginally activates TRPM2. For fully liganded TRPM2, pore opening is intrinsically endothermic, due to ~10-fold larger activation enthalpy for opening (~200 kJ/mol) than for closure (~20 kJ/mol). However, the te

SUBMITTER: Bartok A 

PROVIDER: S-EPMC9881722 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature