Guo-Dong Li, David C. Chiara, Gregory W. Sawyer, S. Shaukat Husain, Richard W. Olsen, and Jonathan B. Cohen
Anesthesia has revolutionized medicine since its introduction in 1846. But the molecular workings of the responsible agents have remained surprisingly elusive. This week, Li et al. tackled the problem using photoaffinity labeling, a technique for labeling binding sites on proteins. Because most general anesthetics enhance the activity of GABAA receptors, the authors photolabeled GABAA receptors, purified from bovine cortex, with a photoreactive analog of the intravenous anesthetic etomidate. By protein microsequencing, they identified two labeled methionines. GABAA receptors are heteromers of five subunits each having extracellular domains and four membrane-spanning domains (M14). One photolabeled methionine was in the M1 region of the a subunit and the other was in M3 of the subunit. Structural models predict that the anesthetic site is a water-filled pocket located in the same subunit interface as the GABA binding site in the extracellular domain, some 50 away. The perfect place for an allosteric modulatory site, it would seem.
Manavu Tohmi, Hiroki Kitaura, Seiji Komagata, Masaharu Kudoh, and Katsuei Shibuki
Several tricks have been used to map brain activity noninvasively, thus avoiding potentially toxic dyes and manipulation of the tissue. This week, Tohmi et al. report on a noninvasive imaging technique that is powered by mitochondria. The authors compared the well studied intrinsic optical imaging method to that of endogenous flavoprotein fluorescence, the latter of which relies on activity-induced changes in the fluorescence of mitochondrial flavoproteins. The authors measured transcranial fluorescence in the visual cortex of anest