Photoactivatable AMPA for the study of glutamatergic neuronal transmission using two-photon excitation. Issue 25 (4th June 2021)

• Record Type: Journal Article
• Authors: Deodato, Davide; Asad, Naeem; Dore, Timothy M.
• Is Part Of: Organic & biomolecular chemistry. Volume 19:Issue 25(2021)
• Page Start: 5589
• Page End: 5594
• Publication Date: 2021-06-04
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/d1ob01006a
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : TMP-CyHQ-AMPA is a photoactivatable form of a glutamate receptor agonist that has high sensitivity to 2-photon excitation. It can be used to study glutamatergic transmission with exceptional spatial-temporal resolution in complex tissue preparations. Abstract : We report a photoactivatable agonist of the AMPA subtype of ionotropic glutamate receptors, TMP-CyHQ-AMPA, which was designed to study the fast excitatory transmission between neurons. Upon visible light excitation, TMP-CyHQ-AMPA quantitatively released AMPA in high quantum yield on an ultra-short timescale. Intriguingly, the photolyisis can be carried out using 2-photon excitation (2PE) with remarkable efficiency, giving a two-photon uncaging action cross section ( δ u ) value of 1.71 GM. TMP-CyHQ-AMPA is soluble in pysiological buffer and no hydrolysis was detected in the absence of light. Molecular docking experiments indicated that the photocaging strategy abolishes the affinity of AMPA for the GluR2 receptor and no GABAergic effects (as commonly observed in caged glutamates) are expected. TMP-CyHQ-AMPA can be used to study glutamatergic neuronal transmission with exceptional spatial-temporal resolution in complex tissue preparations.