The mechanosensitive channel TMEM63B contributes to noxious heat sensation in the dorsal root ganglia
Year: 2026
Type: article
Abstract: In mammals, heat sensation is primarily mediated by thermosensitive channels, particularly transient receptor potential (TRP) channels, in dorsal root ganglion (DRG) neurons. However, whether additional channels contribute to noxious heat detection remains unclear. Here, we investigated the role of the mechanosensitive cation channel TMEM63B in DRG neurons and unexpectedly discovered its involvement in noxious thermosensation rather than mechanosensation. TMEM63B was broadly expressed in DRG neurons, and its global knockout or DRG-specific conditional knockout markedly reduced heat sensitivity. Deletion of TMEM63B significantly attenuated heat-induced calcium responses and currents in DRG neurons and elevated the temperature threshold for action potential initiation. Recombinant TMEM63B exhibited moderate heat response in calcium imaging assays. Notably, in the presence of arachidonic acid, TMEM63B was strongly activated by heat, suggesting that its thermosensitivity is modulated by the membrane lipid environment. Together, these findings identify TMEM63B as a novel channel contributing to heat sensation and reveal a lipid-dependent modulation of its channel activity.
Source: PLoS Biology
Language: English
Topic: Ion Channels and Receptors
Subfield: Sensory Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,500
Funders: National Natural Science Foundation of China, Natural Science Foundation of Jiangsu Province, National Key Research and Development Program of China, Fundamental Research Funds for the Central Universities, Special Fund Project for Science and Technology Innovation Strategy of Guangdong Province
OpenAlex ID: W7222468544