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- W3214289898 endingPage "5591" @default.
- W3214289898 startingPage "5575" @default.
- W3214289898 abstract "At chemical synapses, synaptic vesicles release their acidic contents into the cleft, leading to the expectation that the cleft should acidify. However, fluorescent pH probes targeted to the cleft of conventional glutamatergic synapses in both fruit flies and mice reveal cleft alkalinization rather than acidification. Here, using a reaction-diffusion scheme, we modeled pH dynamics at the Drosophila neuromuscular junction as glutamate, ATP, and protons (H+) were released into the cleft. The model incorporates bicarbonate and phosphate buffering systems as well as plasma membrane calcium-ATPase activity and predicts substantial cleft acidification but only for fractions of a millisecond after neurotransmitter release. Thereafter, the cleft rapidly alkalinizes and remains alkaline for over 100 ms because the plasma membrane calcium-ATPase removes H+ from the cleft in exchange for calcium ions from adjacent pre- and postsynaptic compartments, thus recapitulating the empirical data. The extent of synaptic vesicle loading and time course of exocytosis have little influence on the magnitude of acidification. Phosphate but not bicarbonate buffering is effective at suppressing the magnitude and time course of the acid spike, whereas both buffering systems are effective at suppressing cleft alkalinization. The small volume of the cleft levies a powerful influence on the magnitude of alkalinization and its time course. Structural features that open the cleft to adjacent spaces appear to be essential for alleviating the extent of pH transients accompanying neurotransmission." @default.
- W3214289898 created "2021-11-22" @default.
- W3214289898 creator A5039111030 @default.
- W3214289898 creator A5043233902 @default.
- W3214289898 creator A5045516241 @default.
- W3214289898 creator A5065585057 @default.
- W3214289898 creator A5069387932 @default.
- W3214289898 creator A5087300539 @default.
- W3214289898 creator A5089418861 @default.
- W3214289898 date "2021-12-01" @default.
- W3214289898 modified "2023-09-29" @default.
- W3214289898 title "Computational modeling predicts ephemeral acidic microdomains in the glutamatergic synaptic cleft" @default.
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