RESEARCH ARTICLE
Molecular Mechanisms of TRPV1 Channel Activation
Andrés Jara-Oseguera1, Andrés Nieto-Posadas2, Arpad Szallasi3, 4, León D. Islas1, Tamara Rosenbaum*, 2
Article Information
Identifiers and Pagination:
Year: 2010Volume: 3
First Page: 68
Last Page: 81
Publisher ID: TOPAINJ-3-68
DOI: 10.2174/1876386301003010068
Article History:
Received Date: 07/09/2009Revision Received Date: 21/09/2009
Acceptance Date: 18/08/2010
Electronic publication date: 28/9/2010
Collection year: 2008
open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Transient Receptor Potential (TRP) cation channels participate in various fundamental processes in cell- andorganism-physiology in unicellular eukaryotes, invertebrates and vertebrates. Interestingly, many TRP channels function as detectors of sensory stimuli. The TRPV1 (vanilloid 1) channel serves as an integrator of noxious chemical and physical stimuli known to cause irritation and pain, such as elevated temperatures, acids, and irritant chemical compounds, and its activation has been linked to acute nociceptive pain and neurogenic inflammation. The mechanisms by which the channel detects incoming stimuli, how the sensing domains are coupled to channel gating and how these processes are connected to specific structural regions in the channel are not fully understood, but valuable information is available. Many sites involved in agonist detection have been characterized and gating models that describe many features of the channel’s behavior have been put forward. Structural and functional information indicates TRP channels are similar to voltage-activated potassium channels, with a tetrameric organization and six-transmembrane-region subunits, a pore domain with multi-ion binding properties and an intracellular S6 gate that seems to be the point of convergence of the many activation modalities leading to the opening of the ion conduction pathway. Furthermore, TRPV1 expression is altered in various disease states and TRPV1 gene polymorphism was speculated to play a role in pain sensation. The complex activation and regulation of TRPV1 may have important implications for drug development
