We identified a fluorophore, 1-aminoanthracene (1-AMA), that is anesthetic, potentiates GABAergic transmission, and gives an appropriate dissociation constant, Kd Ϸ 0. ferritin ͉ probe ͉ GABA ͉ propofol ͉ imaging

The authors note that in Fig. 1 the alignment of the nicotinic receptor ␣1 subunit sequences (Torpedo californica and rat) in the loop C region with the GABA A receptor ␤ subunit sequences aligns Y190 and T191 of the former with K196 and K197 of the latter. The alignment should align H186 and W197 of the nicotinic receptor with K196 and K197 of the GABA A receptor. The nicotinic sequence that reads VYYTCCPD 195 should read WKHW..YT 191. The error does not alter the conclusions of this article. The corrected figure and its legend appear below. MEDICAL SCIENCESCorrection for ''Abnormal integrin-mediated regulation of chronic myelogenous leukemia CD34 ϩ cell proliferation: BCR/ ABL up-regulates the cyclin-dependent kinase inhibitor, p27 Kip , which is relocated to the cell cytoplasm and incapable of regulating cdk2 activity,''

Plasmid vectors used for mammalian expression or for in vitro cRNA translation can differ substantially and are rarely cross-compatible. To make comparisons between mammalian and Xenopus oocyte expression systems, it would be advantageous to use a single vector without the need for shuttle vectors or subcloning. We have designed such a vector, designated pUNIV for universal, with elements that will allow for in vitro or ex vivo expression in multiple cell types. We tested the expression of pUNIV-based cDNA cassettes using enhanced green fluorescent protein and two forms of the type A γ-aminobutyric acid receptor (GABA A R) and compared pUNIV to vectors optimized for expression in either Xenopus oocytes or mammalian cells. In HEK293 cells, radioligand binding was robust, and patch clamp experiments showed that subtle macroscopic GABA A R kinetics were indistinguishable from our previous results. In Xenopus oocytes, agonist median effective concentration measurements matched previous work using a vector optimized for oocyte expression. Furthermore, we found that expression using pUNIV was significantly enhanced in oocytes and was remarkably long-lasting in both systems.

Background: Structural elements and protein movements underlying GABA A receptor activation are not completely resolved. Results: Glycine insertions in the extracellular ␤4-␤5 linker decrease GABA activation, invert antagonist efficacy, and reduce allosteric modulation. Conclusion: ␤4-␤5 linker is critical for mediating actions of GABA A receptor orthosteric and allosteric ligands. Significance: Detailed structural-functional understanding of GABA A receptor activation is key to understanding its modulation in diseased and healthy states.

No abstract