Effects of capsaicin on VGSCs in TRPV1−/− mice

• Published in: Brain research 2007-08, Vol.1163, p.33-43
• Main Authors: Cao, Xuehong, Cao, Xuesong, Xie, Hong, Yang, Rong, Lei, Gang, Li, Fen, Li, Ai, Liu, Changjin, Liu, Lieju
• Format: Article
• Language: English
• Subjects: Analgesics, Non-Narcotic - pharmacology; Animals; Biological and medical sciences; Capsaicin; Capsaicin - pharmacology; Cell membranes. Ionic channels. Membrane pores; Cell structures and functions; Cells, Cultured; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Drug Interactions; Electric Stimulation; Fundamental and applied biological sciences. Psychology; Knockout mice; Local anesthetics; Membrane Potentials - drug effects; Membrane Potentials - physiology; Membrane Potentials - radiation effects; Mice; Mice, Inbred C57BL; Mice, Knockout; Molecular and cellular biology; Neurology; Neurons - drug effects; Neurons - physiology; Patch-Clamp Techniques - methods; Sodium Channel Blockers - pharmacology; Sodium Channels - drug effects; Tetrodotoxin - pharmacology; Trigeminal Ganglion - cytology; TRPV Cation Channels - deficiency; Voltage gated sodium channel; Whole-cell clamp
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2007.04.085

Abstract 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 μM 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.