Abstract
Glutamate is released from synaptic vesicles following formation of a fusion pore, connecting the vesicle interior with the synaptic cleft. Release is proposed to result from either full fusion of the vesicle with the terminal membrane or by ‘kiss-and-run,’ where release occurs through the fusion pore. ‘Kiss-and-run’ seems implausible as passive diffusion of glutamate through the pore is too slow to account for the rapidity of release. Vesicular accumulation of glutamate is driven by a proton gradient, resulting in the co-release of protons during exocytosis. We tested whether the proton gradient between the vesicle and cleft contributes to glutamate exocytosis. Collapse of the gradient reduced hippocampal glutamatergic transmission, an effect that was not associated with presynaptic changes in excitability, transmitter release probability, or postsynaptic sensitivity. These data indicate that approximately half of glutamate release utilizes the proton gradient between vesicle and cleft, suggesting a significant proportion of release by ‘kiss-and-run.’
Highlights
The amino acid l-glutamate mediates the vast majority of excitatory transmission in the vertebrate central nervous system
The presence of an H+ gradient to release glutamate can only be utilized if release occurs through the narrow fusion pore, with modeling showing that the coefflux of a counter-charged ion will facilitate the release of a charged neurotransmitter through the fusion pore (Khanin et al, 1994, 1997)
The first EPSC evoked after treatment with either extracellular pH6 aCSF or FCCP was reduced by approximately two-thirds compared with control
Summary
The amino acid l-glutamate mediates the vast majority of excitatory transmission in the vertebrate central nervous system. Transmitter release from synaptic vesicles into the synaptic cleft was classically thought to occur following formation of a fusion pore that dilated to result in full vesicle fusion with the presynaptic membrane This process is considered to be responsible for the omega-shaped profile of membranes observed in ultra-structural investigations of the release sites of presynaptic terminals (Heuser, 1989). It has been proposed that vesicles can remain intact, with release occurring through a transient fusion pore, which can close to produce incomplete exocytosis of the vesicle contents. This is often referred to as ‘kiss-and-run’ exocytosis (An and Zenisek, 2004)
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