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Photoswitchable fatty acids enable optical control of TRPV1
An article in the Nature Communications journal presents how photoswitchable fatty acids enable optical control of TRPV1. The aim of this study was to demonstrate that photolipid analogues (FAAzos) could serve as second messengers to control lipid-modulated biological targets like TRPV1, through spatial and temporal application of light. As one of the first experiments of its kind, documenting this procedure sets groundwork for more prospective uses of this budding concept in combining photopharmacology with lipid signaling.
The FAAzos featured in this experiment were modified to resemble the vanilloid capsaicin, which comprises the pungent aspect of chili peppers and is one of the best known agonists for the non-selective TRPV1 (transient receptor potential ion channel) expressed in subpopulations of sensory nerve fibers. The azo-capsaicin FAAzo derivatives (AzCAs) contained an azobenzene photoswitch along their FA chains that rendered the AzCA synthetic signaling molecules inactive in the dark, and active upon irradiation with ultraviolet-A light. One of the various methods used to test the efficacy of these AzCAs on TRPV1 was to observe AzCA activity in wild-type (wt) mouse dorsal root ganglia (DRG) through whole-cell patch clamp electrophysiology and Cal-520 intracellular calcium imaging. After establishing AzCA4-induced TRPV1 activation the next step was to define various applications for AzCA4. This was achieved in one way by monitoring the calcium response of DRG neurons treated with inflammatory agents serotonin and BK which were expected to sensitize TRPV1 more to AzCA4. When this hypothesis was confirmed, it suggested that AzCA4 could be used as a tool to study TRPV1 response to inflammatory pain.
The study also later validated that AzCA4 could be paired with genetically encoded calcium indicators, but such procedures are known to be meticulous in the process of creating the transgenic model of choice. Cal-520 is a relatively convenient and robust calcium indicator that can be easily applied to various protocols. This study is a prime example that Cal-520 is suitable for detecting neural activity and may be used at low concentrations (5 µM) for successful calcium imaging.
The FAAzos featured in this experiment were modified to resemble the vanilloid capsaicin, which comprises the pungent aspect of chili peppers and is one of the best known agonists for the non-selective TRPV1 (transient receptor potential ion channel) expressed in subpopulations of sensory nerve fibers. The azo-capsaicin FAAzo derivatives (AzCAs) contained an azobenzene photoswitch along their FA chains that rendered the AzCA synthetic signaling molecules inactive in the dark, and active upon irradiation with ultraviolet-A light. One of the various methods used to test the efficacy of these AzCAs on TRPV1 was to observe AzCA activity in wild-type (wt) mouse dorsal root ganglia (DRG) through whole-cell patch clamp electrophysiology and Cal-520 intracellular calcium imaging. After establishing AzCA4-induced TRPV1 activation the next step was to define various applications for AzCA4. This was achieved in one way by monitoring the calcium response of DRG neurons treated with inflammatory agents serotonin and BK which were expected to sensitize TRPV1 more to AzCA4. When this hypothesis was confirmed, it suggested that AzCA4 could be used as a tool to study TRPV1 response to inflammatory pain.
The study also later validated that AzCA4 could be paired with genetically encoded calcium indicators, but such procedures are known to be meticulous in the process of creating the transgenic model of choice. Cal-520 is a relatively convenient and robust calcium indicator that can be easily applied to various protocols. This study is a prime example that Cal-520 is suitable for detecting neural activity and may be used at low concentrations (5 µM) for successful calcium imaging.
References
- James Allen Frank , Mirko Moroni, Rabih Moshourab, Martin Sumser, Gary R. Lewin, and Dirk Trauner. Photoswitchable fatty acids enable optical control of TRPV1. Nature Communications, 2015, May, 6:7118, DOI: 10.1038/ncomms8118
- Cal-520®; AM. AAT Bioquest, n.d. Web. 8 June 2016
Original created on November 25, 2016, last updated on October 20, 2022
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