Neurotransmitter depletion by bafilomycin is promoted by vesicle turnover

Accumulation of neurotransmitter into synaptic vesicles is powered by the vacuolar proton ATPase. We show here that, in brain slices, application of the H+-ATPase inhibitors bafilomycin or concanamycin does not efficiently deplete glutamatergic vesicles of transmitter unless vesicle turnover is increased. Simulations of vesicle energetics suggest either that bafilomycin and concanamycin act on the H+-ATPase from inside the vesicle, or that the vesicle membrane potential is maintained after the H+-ATPase is inhibited.