Synthesis of desformylflustrabromine and its evaluation as an alpha4beta2 and alpha7 nACh receptor modulator.

Desformylflustrabromine (dFBr; 1) and desformylflustrabromine-B (dFBr-B; 2) have been previously isolated from natural sources, and the former has been demonstrated to be a novel and selective positive allosteric modulator of alpha4beta2 nicotinic acetylcholine (nACh) receptors. The present study describes the synthesis of water-soluble salts of 1 and 2, and confirms and further investigates the actions of 1 and 2 using two-electrode voltage clamp recordings.

Evidence that fast exocytosis can be predominantly mediated by vesicles not docked at active zones in frog saccular hair cells.

The prevailing model of neurotransmitter release stipulates that Ca2+ influx triggers the rapid fusion of vesicles that are docked at presynaptic active zones. Under this model, slower tonic release is supported by vesicles clustered nearby that have to translocate to the release sites before fusion. We have examined this hypothesis at the afferent synapse of saccular hair cells of the leopard frog, Rana pipiens.

Atomic resolution structures and the mechanism of ion pumping in bacteriorhodopsin.

A structure-based approach to the mechanism of ion pumping in bacteriorhodopsin (BR) has fostered new hypotheses for the detailed molecular changes that underlie ion transport in this light-driven pump. Isomerization of the retinal from all-trans to 13-cis in response to absorption of the energy of a photon is thought to lead to proton transfer from the initially protonated Schiff base to an anionic aspartate residue (Asp85) in the first half of the BR photocycle. In this traditional view the proton is transferred directly from the Schiff base to Asp85.