STIM1 and ORAI1 form a novel cold transduction mechanism in sensory and sympathetic neurons

• DOI: 10.15252/embj.2022111348
• Publication Date: 2022-12-16T08:33:08Z
• Authors: Tamara J Buijs; Bruno Vilar; Chun‐Hsiang Tan; Peter A McNaughton
• Keywords: Orai1; Transduction (biophysics)

Abstract Moderate coolness is sensed by TRPM8 ion channels in peripheral sensory nerves, but the mechanism which noxious cold detected remains elusive. Here, we show that somatosensory and sympathetic neurons express two distinct mechanisms to detect cold. In first, inhibition of a background outward current causes membrane depolarization activates an inward through voltage‐dependent calcium (Ca V ) channels. A second cold‐activated independent voltage, inhibited blockers ORAI downregulation STIM1, recapitulated HEK293 cells co‐expression ORAI1 STIM1. Using total internal reflection fluorescence microscopy found STIM1 aggregate with activate channels, similar underlying store‐operated entry (SOCE), directly activated not emptying stores. This novel may explain phenomenon cold‐induced vasodilation (CIVD), extreme increases blood flow order preserve integrity tissues.