6533b831fe1ef96bd1298e94

RESEARCH PRODUCT

Capsaicin differentially modulates voltage-activated calcium channel currents in dorsal root ganglion neurones of rats

subject

description

It is discussed whether capsaicin, an agonist of the pain mediating TRPV1 receptor, decreases or increases voltage-activated calcium channel (VACC) currents (ICa(V)). ICa(V) were isolated in cultured dorsal root ganglion (DRG) neurones of rats using the whole cell patch clamp method and Ba 2+ as charge carrier. In large diameter neurones (>35Am), a concentration of 50AM was needed to reduce ICa(V) (activated by depolarizations to 0 mV) by 80%, while in small diameter neurones (30Am), the IC50 was 0.36 AM. This effect was concentration dependent with a threshold below 0.025 AM and maximal blockade (>80%) at 5AM. The current–voltage relation was shifted to the hyperpolarized direction with an increase of the current between 40 and 10mVand a decrease between 0 and +50 mV. Isolation of L-, N-, and T-type calcium channels resulted in differential effects when 0.1 AM capsaicin was applied. While T-type channel currents were equally reduced over the voltage range, L-type channel currents were additionally shifted to the hyperpolarized direction by 10 to 20 mV. Ntype channel currents expressed either a shift (3 cells) or a reduction of the current (4 cells) or both (3 cells). Thus, capsaicin increases ICa(V) at negative and decreases ICa(V) at positive voltages by differentially affecting L-, N-, and T-type calcium channels. These effects of capsaicin on different VACCs in small DRG neurones, which most likely express the TRPV1 receptor, may represent another mechanism of action of the pungent substance capsaicin in addition to opening of TRPV1. D 2005 Elsevier B.V. All rights reserved. Theme: Sensory systems Topic: Pain modulation: pharmacology