Dataset Information

Effects of TRPV1 Activation by Capsaicin and Endogenous N-Arachidonoyl Taurine on Synaptic Transmission in the Prefrontal Cortex.

ABSTRACT: While the transient receptor potential vanilloid 1 (TRPV1) ion channel, a non-selective calcium-permeable cation channel with high Ca2+ permeability, mainly integrates physical and chemical stimuli for nociception, recent studies suggest that it has a role beyond a noxious thermal sensor. In fact, TRPV1 is presently being considered as a target for treating pathophysiological processes including pain, fear, and anxiety disorders. Although this ion channel has many potential roles, its underlying mechanism of action remains elusive. Here we show in mice that activation of TRPV1-, by the exogenous agonist capsaicin-, regulates synaptic activity in both glutamatergic and GABAergic synaptic transmission. Moreover, activation by the endogenous activator N-arachidonoyl taurine (NAT), induced similar effects as capsaicin. On the other hand, taurine, the decomposition product of NAT, strongly depressed the evoked glutamatergic synaptic transmission. In addition to these findings, we also show the immunohistochemical distribution of TRPV1 in the prefrontal cortex (PFC) of mice, as such studies are currently less frequent in the PFC. Overall, these observations allow for a better understanding of how TRPV1 helps regulate excitatory and inhibitory synaptic activity in the PFC of mice.

SUBMITTER: Zhang M

PROVIDER: S-EPMC7020858 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Effects of TRPV1 Activation by Capsaicin and Endogenous N-Arachidonoyl Taurine on Synaptic Transmission in the Prefrontal Cortex.

Zhang Mingyue M Ruwe David D Saffari Roja R Kravchenko Mykola M Zhang Weiqi W

Frontiers in neuroscience 20200207

While the transient receptor potential vanilloid 1 (TRPV1) ion channel, a non-selective calcium-permeable cation channel with high Ca<sup>2+</sup> permeability, mainly integrates physical and chemical stimuli for nociception, recent studies suggest that it has a role beyond a noxious thermal sensor. In fact, TRPV1 is presently being considered as a target for treating pathophysiological processes including pain, fear, and anxiety disorders. Although this ion channel has many potential roles, its ...[more]

PMID: 32116530

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Project description:TRPV1 ion channels mediate the response to painful heat, extracellular acidosis, and capsaicin, the pungent extract from plants in the Capsicum family (hot chili peppers) (Szallasi, A., and P.M. Blumberg. 1999. Pharmacol. Rev. 51:159-212; Caterina, M.J., and D. Julius. 2001. Annu. Rev. Neurosci. 24:487-517). The convergence of these stimuli on TRPV1 channels expressed in peripheral sensory nerves underlies the common perceptual experience of pain due to hot temperatures, tissue damage and exposure to capsaicin. TRPV1 channels are nonselective cation channels (Caterina, M.J., M.A. Schumacher, M. Tominaga, T.A. Rosen, J.D. Levine, and D. Julius. 1997. Nature. 389:816-824). When activated, they produce depolarization through the influx of Na+, but their high Ca2+ permeability is also important for mediating the response to pain. In particular, Ca2+ influx is thought to be required for the desensitization to painful sensations over time (Cholewinski, A., G.M. Burgess, and S. Bevan. 1993. Neuroscience. 55:1015-1023; Koplas, P.A., R.L. Rosenberg, and G.S. Oxford. 1997. J. Neurosci. 17:3525-3537). Here we show that in inside-out excised patches from TRPV1 expressed in Xenopus oocytes and HEK 293 cells, Ca2+/calmodulin decreased the capsaicin-activated current. This inhibition was not mimicked by Mg2+, reflected a decrease in open probability, and was slowly reversible. Furthermore, increasing the calmodulin concentration in our patches by coexpression of wild-type calmodulin with TRPV1 produced inhibition by Ca2+ alone. In contrast, patches excised from cells coexpressing TRPV1 with a mutant calmodulin did not respond to Ca2+. Using an in vitro calmodulin-binding assay, we found that TRPV1 in oocyte lysates bound calmodulin, although in a Ca2+-independent manner. Experiments with GST-fusion proteins corresponding to regions of the channel NH2-terminal domain demonstrated that a stretch of approximately 30 amino acids adjacent to the first ankyrin repeat bound calmodulin in a Ca2+-dependent manner. The physiological response to pain involves an influx of Ca2+ through TRPV1. Our results indicate that this Ca2+ influx may feed back on the channels, inhibiting their gating. This type of feedback inhibition could play a role in the desensitization produced by capsaicin.

Dataset Information

Effects of TRPV1 Activation by Capsaicin and Endogenous N-Arachidonoyl Taurine on Synaptic Transmission in the Prefrontal Cortex.

Publications

Effects of TRPV1 Activation by Capsaicin and Endogenous N-Arachidonoyl Taurine on Synaptic Transmission in the Prefrontal Cortex.

Similar Datasets

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