Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 106, Issue 16, Pages 6501-6506Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0810590106
Keywords
ferritin; probe; GABA; propofol; imaging
Categories
Funding
- National Science Foundation [CHE-0548188]
- National Center for Research Resources [1S10-RR-021113-01]
- Henry and Camille Dreyfus Teacher-Scholar award
- National Institutes of Health [GM51595, GM55876, GM47818, NS056411]
- University of Pennsylvania Institute for Medicine and Engineering Seed
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We identified a fluorophore, 1-aminoanthracene (1-AMA), that is anesthetic, potentiates GABAergic transmission, and gives an appropriate dissociation constant, K-d approximate to 0.1 mM, for binding to the general anesthetic site in horse spleen apoferritin (HSAF). 1-AMA fluorescence is enhanced when bound to HSAF. Thus, displacement of 1-AMA from HSAF by other anesthetics attenuates the fluorescence signal and allows determination of K-d, as validated by isothermal titration calorimetry. This provides a unique fluorescence assay for compound screening and anesthetic discovery. Additional electrophysiology experiments in isolated cells indicate that 1-AMA potentiates chloride currents elicited by GABA, similar to many general anesthetics. Furthermore, 1-AMA reversibly immobilizes stage 45-50 Xenopus laevis tadpoles (EC50 = 16 mu M) and fluorescence micrographs show 1-AMA localized to brain and olfactory regions. Thus, 1-AMA provides an unprecedented opportunity for studying general anesthetic distribution in vivo at the cellular and subcellular levels.
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