Effects of capsaicin on VGSCs in TRPV1−/− mice

• DOI: 10.1016/j.brainres.2007.04.085
• Publication Date: 2007-06-04T11:08:30Z
• Authors: Xuehong Cao; Xuesong Cao; Hong Xie; Rong Yang; Gang Lei; Fen Li; Ai Li; Changjin Liu; Lieju Liu
• Keywords: Mice, Knockout; Neurons; 0303 health sciences; Patch-Clamp Techniques; Dose-Response Relationship, Drug; TRPV Cation Channels; Dose-Response Relationship, Radiation; Tetrodotoxin; Analgesics, Non-Narcotic; Electric Stimulation; Sodium Channels; Membrane Potentials; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Trigeminal Ganglion; Animals; Drug Interactions; Capsaicin; Cells, Cultured; Sodium Channel Blockers

Two different mechanisms by which capsaicin blocks voltage-gated sodium channels (VGSCs) were found by using knockout mice for the transient receptor potential V1 (TRPV1(-/-)). Similar with cultured rat trigeminal ganglion (TG) neurons, the amplitude of tetrodotoxin-resistant (TTX-R) sodium current was reduced 85% by 1 muM capsaicin in capsaicin sensitive neurons, while only 6% was blocked in capsaicin insensitive neurons of TRPV1(+/+) mice. The selective effect of low concentration capsaicin on VGSCs was reversed in TRPV1(-/-) mice, which suggested that this effect was dependent on TRPV1 receptor. The blockage effect of high concentration capsaicin on VGSCs in TRPV1(-/-) mice was the same as that in capsaicin insensitive neurons of rats and TRPV1(+/+) mice. It is noted that non-selective effect of capsaicin on VGSCs shares many similarities with local anesthetics. That is, firstly, both blockages are concentration-dependent and revisable. Secondly, being accompanied with the reduction of amplitude, voltage-dependent inactivation curve shifts to hyperpolarizing direction without a shift of activation curve. Thirdly, use-dependent blocks are induced at high stimulus frequency.