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 mu M) 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.