Structure-function studies of TRPV1 alcohol modulation

The TRPV1 channel is a member of the Transient Receptor Potential (TRP) family of cation channels and is responsible for the perception of different noxious stimuli. It is mainly found in the peripheral terminals of primary sensory neurons where pain is produced and in various brain regions such as hypothalamus, cerebellum and cerebralcortex. It can be activated by a large number of physical and chemical stimuli and themost known ones include capsaicin (the active component of hot chili peppers), noxiousheat (greater than 42◦C), voltage and acidity. There is now evidence of how ethanol can potentiate TRPV1 activity when activatedby low pH (inflammation) and capsaicin, and how it can lower the temperature thresholdactivation when activated by heat. It is also known that different alcohol moleculescan affect many biophysical processes, including the kinetics of ion channels acting aspositive allosteric modulators, therefore, it is important to determine how the proprietiesof such receptors change when alcohol molecules interact with the system. Following this path, the aim of this project is to optimize a protocol which can later be used for a simpler TRPV1 expression on Xenopus laevis oocytes in order to perform experiments of electrophysiology (TEVC). Once this is achieved, using the TEVC method, it will bepossible to determine how alcohol modulates TRPV1 by figuring out the alcohol cut-off size (the maximum size alcohol that can bind and modulate to the channel) that couldindicate a direct alcohol binding site on the channel. Through this step and others that will follow in this direction, a new way of understanding pain can be accomplished by formulating more pain-inhibiting drugs that can act on additional specific sites.