TRPA1 Channels Mediate Cold Temperature Sensing in Mammalian Vagal Sensory Neurons: Pharmacological and Genetic Evidence

• DOI: 10.1523/jneurosci.1696-08.2008
• Publication Date: 2008-07-30T16:38:15Z
• Authors: Otto Fajardo; Victor Meseguer; Carlos Belmonte; Félix Viana
• Keywords: TRPM8; Cold sensitivity; Nodose Ganglion; Nociceptor; Ruthenium red; Capsaicin; Thermoreceptor

Cold thermoreceptors have been described in different territories of the vagus nerve. Application cold temperature to these visceral afferents can evoke major protective reflexes and thermoregulatory responses. However, virtually nothing is known about transduction mechanisms underlying sensitivity vagal afferents. Here, we investigated effects stimulation on intracellular calcium responses excitability cultured sensory neurons rat nodose ganglion. A large fraction were activated by cold, with a mean threshold approximately 24 degrees C. Cooling was accompanied development small inward current firing action potentials. Most cold-sensitive also heat capsaicin, suggesting nociceptive function. The pharmacological response TRPM8 TRPA1 agonists antagonists suggested that, unlike results observed somatic tissues, mediator cold-evoked neurons. Thus, most potentiated cinnamaldehyde, menthol, icilin, BCTC [4-(3-chloro-pyridin-2-yl)-piperazine-1-carboxylic acid (4-tert-butyl-phenyl)-amide], TRPA1, inhibited ruthenium red, camphor, HC03001 [2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide]. Results mouse revealed similar profile Furthermore, experiments knock-out mice showed reduction percentage compared wild-type animals. Together, support an important role channels thermosensation indicate differences signals between