TRPC3 is involved in peripheral sensitization induced by PAR2 and P2Y2 receptors. Intrinsic excitability of a representative DRG nociceptor recorded sequentially under current-clamp conditions (RMP = -67 mV). (A) Firing of action potentials was consistently triggered by current pulses (200 pA; 50 ms duration) injected at fixed time intervals (n = 25). No firing was detected in conditions of subthreshold current injection (50 pA; 50 ms duration) (B) unless the cells were first sensitized by application of both PAR2 agonist AC55541 (100 μM) and P2Y2 agonist UTP (100 μM) (n = 14/25) (C). (D) Treatment with the specific TRPC3 antagonist Pyr10 (10 μM) suppressed this sensitization effect in most neurons (n = 6/9). (E) At the end of each recording, cells were tested for viability and displayed normal firing activity after Pyr10 washout (n = 6).