@article{130421,
  keywords = {Animals, Synaptic Transmission, Molecular Structure, Patch-Clamp Techniques, Interneurons, Photons, Cerebellum, Neurotransmitter Agents, Drug Stability, Evoked Potentials, Phenylacetates, Photochemical Processes, Receptors, GABA, gamma-Aminobutyric Acid},
  author = {Diana Shi and Federico Trigo and Martin Semmelhack and Samuel Wang},
  title = {Synthesis and biological evaluation of bis-CNB-GABA, a photoactivatable neurotransmitter with low receptor interference and chemical two-photon uncaging properties},
  abstract = {<p>Photoactivatable "caged" neurotransmitters allow optical control of neural tissue with high spatial and temporal precision. However, the development of caged versions of the chief vertebrate inhibitory neurotransmitter, γ-amino butyric acid (GABA), has been limited by the propensity of caged GABAs to interact with GABA receptors. We describe herein the synthesis and application of a practically useful doubly caged GABA analog, termed bis-α-carboxy-2-nitrobenzyl-GABA (bis-CNB-GABA). Uncaging of bis-CNB-GABA evokes inward GABAergic currents in cerebellar molecular layer interneurons with rise times of 2 ms, comparable to flash duration. Response amplitudes depend on the square of flash intensity, as expected for a chemical two-photon uncaging effect. Importantly, prior to uncaging, bis-CNB-GABA is inactive at the GABAA receptor, evoking no changes in holding current in voltage-clamped neurons and showing an IC50 of at least 2.5 mM as measured using spontaneous GABAergic synaptic currents. Bis-CNB-GABA is stable in solution, with an estimated half-life of 98 days in the light. We expect that bis-CNB-GABA will prove to be an effective tool for high-resolution chemical control of brain circuits.</p>
},
  year = {2014},
  journal = {J Am Chem Soc},
  volume = {136},
  pages = {1976-81},
  month = {02/2014},
  issn = {1520-5126},
  doi = {10.1021/ja411082f},
  language = {eng},
}