Differential effects of lipopolysaccharide on mouse sensory TRP channels

• Published in: Cell calcium (Edinburgh) 2018-07, Vol.73, p.72-81
• Main Authors: Boonen, Brett, Alpizar, Yeranddy A., Sanchez, Alicia, López-Requena, Alejandro, Voets, Thomas, Talavera, Karel
• Format: Article
• Language: English
• Subjects: Animals; Calcium - metabolism; Cells, Cultured; Dose-Response Relationship, Drug; Endotoxin; Ganglia, Spinal - drug effects; Ganglia, Spinal - metabolism; HEK293 Cells; Humans; Lipopolysaccharides - pharmacology; LPS; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Sensory neuron; TRPA1; TRPA1 Cation Channel - agonists; TRPA1 Cation Channel - metabolism; TRPM3; TRPM8; TRPV Cation Channels - agonists; TRPV Cation Channels - metabolism; TRPV1
• ISSN: 0143-4160; 1532-1991
• DOI: 10.1016/j.ceca.2018.04.004

[Display omitted] •LPS activates heterologous TRPV1, TRPM3 and TRPM8, but not TRPV2.•TRPV1 activation by LPS is independent of residues conferring capsaicin sensitivity.•Low temperatures facilitate TRPM8 activation by LPS.•Stimulation of mouse sensory neurons by LPS is mainly mediated by TRPA1 and TRPV1.•Sensory TRP channels emerge as newly-described effectors of bacterial endotoxins. Acute neurogenic inflammation and pain associated to bacterial infection have been traditionally ascribed to sensitization and activation of sensory nerve afferents secondary to immune cell stimulation. However, we recently showed that lipopolysaccharides (LPS) directly activate the Transient Receptor Potential channels TRPA1 in sensory neurons and TRPV4 in airway epithelial cells. Here we investigated whether LPS activates other sensory TRP channels expressed in sensory neurons. Using intracellular Ca2+ imaging and patch-clamp we determined the effects of LPS on recombinant TRPV1, TRPV2, TRPM3 and TRPM8, heterologously expressed in HEK293T cells. We found that LPS activates TRPV1, although with lower potency than for TRPA1. Activation of TRPV1 by LPS was not affected by mutations of residues required for activation by electrophilic agents or by diacylglycerol and capsaicin. On the other hand, LPS weakly activated TRPM3, activated TRPM8 at 25 °C, but not at 35 °C, and was ineffective on TRPV2. Experiments performed in mouse dorsal root ganglion (DRG) neurons revealed that genetic ablation of Trpa1 did not abolish the responses to LPS, but remain detected in 30% of capsaicin-sensitive cells. The population of neurons responding to LPS was dramatically lower in double Trpa1/Trpv1 KO neurons. Our results show that, in addition to TRPA1, other TRP channels in sensory neurons can be targets of LPS, suggesting that they may contribute to trigger and regulate innate defenses against gram-negative bacterial infections.