Effects of capsaicin on VGSCs in TRPV1-/- mice.
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.
Cao
Xuehong
X
Department of Physiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Cao
Xuesong
X
Xie
Hong
H
Yang
Rong
R
Lei
Gang
G
Li
Fen
F
Li
Ai
A
Liu
Changjin
C
Liu
Lieju
L
D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects*; D050916:TRPV Cation Channels / Q000172:deficiency*; D013779:Tetrodotoxin / Q000494:pharmacology; D012668:Trigeminal Ganglion / Q000166:cytology
D018712:Analgesics, Non-Narcotic; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D013779:Tetrodotoxin; D002211:Capsaicin