Effect of TRPM8 knockdown on TTR-induced calcium influx. TRPM8 channels are necessary for L55P-induced calcium influx. Representative images of DRG neurons loaded with (A) non-specific control siRNA elicited a greater L55P-induced calcium influx (ΔF/F0) than growth cones loaded with (B) specific TRPM8 siRNA (#57381). (C) Pooled results show calcium influx (ΔF/F0) in response to L55P for control siRNA (closed circles, n = 12) and a specific TRPM8 siRNA (open circles, n = 16) from 3 separate experiments. (D) Using 3 different TRPM8 siRNA oligonucleotides results in a similar reduction in L55P-mediated calcium entry. Significant differences from control are depicted as: *p < 0.05; **p < 0.005; Mann-Whitney U-test. Error bars indicate mean ± SEM. Scale bar is 5 μm.