Spinal activation of TRPV1-mediated attenuation of a chemoreflex: Potential mechanism of action linking TRPV1 activation with modulation of CaV2.2 channels

Abstract

The objective of the present study was to examine the effect of intrathecal injection of the transient receptor potential vanilloid 1 (TRPV1) channel agonist, capsaicin, on the spinal transmission of the pressure reflex induced by intra-arterial administration of capsaicin (chemoreflex). In decerebrated rats, we found that intrathecal injection of capsaicin attenuated significantly the increase in arterial pressure evoked by intra-arterial capsaicin when compared to intrathecal injection of saline. Afterwards, whole-cell patch-clamp technique was employed to determine if TRPV1 activation was involved in the modulation of voltage-gated Ca²⁺ channels (Ca_V2.2) in DiI-labeled sensory neurons innervating the triceps surae muscle. This channel subtype was previously shown to play a key role in the exercise pressor reflex, and is also the major Ca²⁺ ion carrier in sensory neurons innervating the triceps surae muscle. Our results showed that either TRPV1 agonists, capsaicin or olvanil, inhibited Ca_V2.2 currents. The agonist-mediated Ca_V2.2 inhibition was sensitive to the TRPV1 blocker, AMG 517, and absent in sensory neurons isolated from TRPV1 knockout rats. Moreover, in ‘rescue’ experiments, after transfecting sensory neurons from TRPV1 knockout rats with TRPV1 cDNA, application of capsaicin led to Ca_V2.2 inhibition as observed with neurons isolated from wild-type rats. These data suggest that the decrease of the pressor response following intrathecal capsaicin-mediated stimulation appears to involve a mechanism of action linking TRPV1 activation with Ca_V2.2 current inhibition.