Surface-accessible GABA supports tonic and quantal synaptic transmission

Exocytosis is commonly viewed as the only secretory process able to account for quantal forms of fast synaptic transmission. However, the demonstrated variability and composite properties of miniature postsynaptic signals are not easily explained by all-or-none exocytotic discharge of transmitter in solution from inside vesicles. Recent, studies of endocrine secretion have shown that hormone release does not coincide with exocytosis due to its tr apping in the core matrix of the granule. Thus, we tested whether the synap tic transmitter GABA could also be held in a matrix before being released. Using confocal microscopy and flow cytometry of embryonic rat hippocampal n eurons, we found a GABA immunoreaction at the surface of live cell bodies a nd growth cones that coincided spatially and quantitatively with the bindin g of tetanus toxin fragment, C (TTFC). TTFC binds predominantly at membrane sites containing the trisialoglycosphingolipid GT1b. Using flow cytometry, GT1b-containing Liposomes preincubated in 100 nM GABA exhibited the same r elationship between GABA and TTFC surface binding as found on neurons and g rowth cones. Embryonic neurons differentiated in culture expressed initiall y a tonic, and after 3-5 days, transient, postsynaptic signals mediated by GABA acting at GABA(A)receptor/Cl- channels. A stream of saline applied to the neuronal surface rapidly and reversibly suppressed both tonic and trans ient signals. A brief application of the GABAmimetic isoguvacine immediatel y transformed both tonic and transient GABAergic signals into tonic and tra nsient isoguvacinergic signals. These results and those in the literature a re consistent with an immediately releasable compartment of transmitter acc essible from the presynaptic surface. (C) 2000 Wiley-Liss, Inc.