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.
Cavelier
Pauline
P
Department of Physiology, University College London, Gower Street, London WC1E 6BT, UK.
Attwell
David
D
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D018942:Macrolides / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism*; D014701:Veratridine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D018942:Macrolides; D018377:Neurotransmitter Agents; D015222:Sodium Channels; C057620:bafilomycin A; D018698:Glutamic Acid; D014701:Veratridine; C036978:concanamycin A; D006180:Proton-Translocating ATPases; D011188:Potassium