Figure 3
Combined siRNAs targeted to S1PR1/R2/R3 blocked the S1P-induced increase in excitability. (A) shows representative traces from a neuron treated with the combined short-interfering RNAs (siRNAs) targeted to sphingosine-1-phosphate (S1P)R1/R2/R3 (100 nM each); the trace shown in the left panel was obtained under control conditions whereas that in the right panel was after a 6-min exposure to 1 μM S1P. The dotted lines indicate the 0 mV level. (B) illustrates cells treated with 300 nM negative control siRNA. The left panel shows that under control conditions 4 action potentials (APs) were fired whereas, after a 6-min exposure to 1 μM S1P, the same ramp current elicited 10 APs. (C) summarizes the results obtained from five cells in each treatment group. S1P significantly increased the number of APs in neurons treated with negative control (NC) siRNA at 6 and 10 min. The asterisks (*) represent a significant difference compared to the control (P < 0.05 RM ANOVA with a Holm-Sidak all-pairs test).