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Transient receptor potential A1 (TRPA1) is a nonselective cation channel implicated in thermosensation and inflammatory pain. In this study, we show that TRPA1 (activated by allyl isothiocyanate, acrolein, and 4-hydroxynonenal) elevates the intracellular Ca 2+ concentration ([Ca 2+ ] i ) in dorsal root ganglion (DRG) neurons in the presence and absence of extracellular Ca 2+ Pharmacological and immunocytochemical analyses revealed the presence of TRPA1 channels both on the plasma membrane and in endolysosomes. Confocal line-scan imaging demonstrated Ca 2+ signals elicited from individual endolysosomes ("lysosome Ca 2+ sparks") by TRPA1 activation. In physiological solutions, the TRPA1-mediated endolysosomal Ca 2+ release contributed to ∼40% of the overall [Ca 2+ ] i rise and directly triggered vesicle exocytosis and calcitonin gene-related peptide release, which greatly enhanced the excitability of DRG neurons. Thus, in addition to working via Ca 2+ influx, TRPA1 channels trigger vesicle release in sensory neurons by releasing Ca 2+ from lysosome-like organelles.

Intracellular TRPA1 mediates Ca2+ release from lysosomes in dorsal root ganglion neurons