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Effects of capsaicin on VGSCs in TRPV1-/- mice
Xuehong Cao1, Xuesong Cao, Hong Xie
1Department of Physiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
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 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.
Insights
Capsaicin blocks voltage-gated sodium channels (VGSCs) via two mechanisms. One TRPV1 receptor-dependent mechanism is seen at low concentrations, while high concentrations show a non-selective block similar to local anesthetics.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Voltage-gated sodium channels (VGSCs) are crucial for neuronal excitability.
- Capsaicin, known for its TRPV1 receptor interaction, also affects VGSCs.
Purpose of the Study:
- To elucidate the distinct mechanisms by which capsaicin modulates VGSCs.
- To investigate the role of the TRPV1 receptor in capsaicin's blockade of VGSCs.
Main Methods:
- Utilized TRPV1 knockout (TRPV1(-/-)) mice and wild-type (TRPV1(+/+)) mice.
- Electrophysiological recordings in cultured rat trigeminal ganglion (TG) neurons.
- Applied varying concentrations of capsaicin to assess blockade effects.
Main Results:
- Low concentration capsaicin selectively blocked tetrodotoxin-resistant (TTX-R) sodium current in a TRPV1-dependent manner.
- High concentration capsaicin induced a non-selective blockade of VGSCs, irrespective of TRPV1 status.
- The non-selective blockade exhibited characteristics similar to local anesthetics, including concentration-dependence, reversibility, and use-dependent effects.
Conclusions:
- Capsaicin employs at least two distinct mechanisms to block VGSCs.
- TRPV1 receptor activation mediates a specific, low-concentration blockade of VGSCs.
- High-concentration capsaicin acts non-selectively on VGSCs, mirroring local anesthetic action.
