Inhibitory Effects of Capsaicin on Voltage-Gated Potassium Channels by TRPV1-Independent Pathway

Previously we observed that capsaicin, a transient receptor potential vanilloid 1 (TRPV1) receptor activator, inhibited transient potassium current (I_A) in capsaicin-sensitive and capsaicin-insensitive trigeminal ganglion (TG) neurons from rats. It suggested that the inhibitory effects of capsaicin on I_A have two different mechanisms: TRPV1-dependent and TRPV1-independent pathways. The main purpose of this study is to further investigate the TRPV1-independent effects of capsaicin on voltage-gated potassium channels (VGPCs). Whole cell patch-clamp technique was used to record I_A and sustained potassium current (I_K) in cultured TG neurons from trpv1 knockout (TRPV1^?/?) mice. We found that capsaicin reversibly inhibited I_A and I_K in a dose-dependent manner. Capsaicin (30 μM) did not alter the activation curve of I_A and I_K but shifted the inactivation–voltage curve to hyperpolarizing direction, thereby increasing the number of inactivated VGPCs at the resting potential. Administrations of high concentrations capsaicin, no use-dependent block, and delay of recovery time course were found on I_K and I_A. Moreover, forskolin, an adenylate cyclase agonist, selectively decreased the inhibitory effects of I_K by capsaicin, whereas none influenced the inhibitions of I_A. These results suggest that capsaicin inhibits the VGPCs through TRPV1-independent and PKA-dependent mechanisms, which may contribute to the capsaicin-induced nociception.