Figure 8.
Functional evidence suggesting alternative thermo-TRP channels present in vagal afferents. (A, upper panel) Representative calcium trace from cultured vagal afferent cell bodies showing menthol fails to activate at concentrations selective for TRPM8, but produce large calcium transients at concentrations known to activate TRPV3. (A, lower panel) Average concentration response relationship for menthol induced increases in cytosolic calcium (N = 7, P < 0.001, ANOVA). Menthol induced calcium increases were significantly reduced with RuR (N = 9, P < 0.001, paired t-test) also consistent with TRPV3 activation. (B, upper panel) Calcium trace showing the concentration-dependent increase in cytosolic calcium by the TRPV3 agonist ethyl vanillin in cultured vagal afferents taken from TRPV1−/− mice. CAP exposure failed to elicit a response as predicted. (B, lower panel) Average concentration response relationship for ethyl vanillin induced increases in cytosolic calcium (N = 5, P = 0.002, ANOVA). (C, upper panel) Left: Calcium trace showing the TRPM3 agonist pregnenolone sulfate concentration-dependently activated a subpopulation of CAP-sensitive vagal afferent neurons. Right: This response was maintained in afferents taken from TRPV1−/− mice. (C, lower panel) Average change in intracellular calcium across concentrations from pregnenolone sulfate responsive neurons from rat (N = 8, P < 0.001, ANOVA) and TRPV1−/− mice (N = 3, P < 0.01, paired T-test). Statistical significance is indicated by an asterisk (*).
