Figure 4

Neurons treated with siRNAs targeted to S1PR₁ and R₃ were not sensitized by S1P but did respond to PGE₂. (A) demonstrates representative traces from a sensory neuron treated with combined siRNAs targeted to S1PR₁ and R₃ (100 nM each); under control conditions, the neuron generated 3 APs. (B) After a 10-min exposure to 1 μM S1P, this neuron fired only 2 APs. (C) A subsequent 10-min exposure to 1 μM PGE₂ resulted in the generation of 13 APs. (D) summarizes the effects of S1P and PGE₂ exposures after treatment with siRNAs targeted to S1PR₁ and R₃. S1P failed to augment AP firing, but PGE₂ significantly increased the number of APs after 14-, 16-, and 20-min exposures. Results were obtained from eight neurons (control through 12 min), seven neurons at 14 min, and six neurons at 16 and 20 min. Asterisks (*) represent a significant difference between those treatments compared to control (P < 0.05, Kruskal-Wallis ANOVA on ranks with Dunn’s post hoc test). AP - action potential, Cont - control, PGE₂ - prostaglandin E₂, S1P - sphingosine-1-phosphate.