TRPC3 is linked to proteases/PAR2 transduction in DRG neurons. (A) Addition of 100 μM AC55541 to the calcium-free perfusion solution activates PAR2 receptors, which initiate both SOCE and ROCE responses. Treatment with Gd3+ removed the Orai component, which produced a small but non-significant decrease in calcium influx (n = 22-24, P > 0.05). (B) The selective inhibition of TRPC3 with Pyr10 (10 μM, 15 min) resulted in a drastic decrease (66%) of AC55541-evoked calcium entry (n = 19-29, P < 0.001). (C) shRNA-mediated knockdown of TRPC3 induced a similar decrease in PAR2-mediated calcium entry of approximately 66% (n = 24-73, P < 0.0001). (D) Heterologous overexpression of TRPC3 (OE) increased by 135% the calcium influx following PAR2 activation, indicating a strong link between TRPC3 activity and PAR2 function (n = 18-26, P < 0.0001).