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• W3173883896 abstract "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 (NMJ) as glutamate, adenosine triphosphate (ATP) and protons (H + ) are released into the cleft. The model incorporates bicarbonate and phosphate buffering systems as well as plasma membrane calcium-ATPase (PMCA) activity and predicts substantial cleft acidification but only for fractions of a millisecond following neurotransmitter release. Thereafter, the cleft rapidly alkalinizes and remains alkaline for over 100 milliseconds, as the PMCA removes H + from the cleft in exchange for calcium ions (Ca 2+ ) from adjacent pre- and post-synaptic compartments; thus recapitulating the empirical data. The extent of synaptic vesicle loading and time course of exocytosis has little influence on the magnitude of acidification. Phosphate, but not bicarbonate buffering is effective at ameliorating the magnitude and time course of the acid spike, while both buffering systems are effective at ameliorating 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 disturbances accompanying neurotransmission. SIGNIFICANCE STATEMENT Acid-base imbalances have surprisingly potent neurological effects highlighting the acute pH sensitivity of many neural mechanisms. Acid-Sensing Ion-Channels (ASICs), which open in response to acid shifts in extracellular pH, are an example of such a mechanism. However, while ASICs open during neurotransmission at conventional glutamatergic synapses, pH-sensitive electrodes and fluorophores show no signs of acidification at these synapses, only alkalinization. To resolve this paradox, we built a computational model which allows a glimpse beyond the experimental limitations of pH-sensitive electrodes and fluorophores. Our model reveals a highly dynamic pH landscape within the synaptic cleft, harboring deep but exceedingly rapid acid transients that give way to a prolonged period of alkalinization, thus reconciling ASIC activation with direct measurements of extracellular pH." @default.
• W3173883896 created "2021-07-05" @default.
• W3173883896 creator A5008616136 @default.
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• W3173883896 date "2021-06-30" @default.
• W3173883896 modified "2023-10-15" @default.
• W3173883896 title "Computational modeling predicts acidic microdomains in the glutamatergic synaptic cleft" @default.
• W3173883896 cites W1506710296 @default.
• W3173883896 cites W1524619698 @default.
• W3173883896 cites W1525038108 @default.
• W3173883896 cites W1537385836 @default.
• W3173883896 cites W1664184517 @default.
• W3173883896 cites W1821391051 @default.
• W3173883896 cites W1947888345 @default.
• W3173883896 cites W1956266132 @default.
• W3173883896 cites W1964212152 @default.
• W3173883896 cites W1970729216 @default.
• W3173883896 cites W1971152332 @default.
• W3173883896 cites W1971582447 @default.
• W3173883896 cites W1977384016 @default.
• W3173883896 cites W1982026643 @default.
• W3173883896 cites W1982117302 @default.
• W3173883896 cites W1982207207 @default.
• W3173883896 cites W1982584364 @default.
• W3173883896 cites W1982682966 @default.
• W3173883896 cites W1983934754 @default.
• W3173883896 cites W2001037643 @default.
• W3173883896 cites W2001279193 @default.
• W3173883896 cites W2001646873 @default.
• W3173883896 cites W2001858901 @default.
• W3173883896 cites W2017384269 @default.
• W3173883896 cites W2021706041 @default.
• W3173883896 cites W2022036407 @default.
• W3173883896 cites W2025828073 @default.
• W3173883896 cites W2026812506 @default.
• W3173883896 cites W2034080784 @default.
• W3173883896 cites W2039489626 @default.
• W3173883896 cites W2040336234 @default.
• W3173883896 cites W2040478973 @default.
• W3173883896 cites W2044211641 @default.
• W3173883896 cites W2045626372 @default.
• W3173883896 cites W2051380496 @default.
• W3173883896 cites W2062533240 @default.
• W3173883896 cites W2063770299 @default.
• W3173883896 cites W2075081518 @default.
• W3173883896 cites W2075238065 @default.
• W3173883896 cites W2076310117 @default.
• W3173883896 cites W2082732103 @default.
• W3173883896 cites W2082969312 @default.
• W3173883896 cites W2084840477 @default.
• W3173883896 cites W2085615315 @default.
• W3173883896 cites W2085805107 @default.
• W3173883896 cites W2086317178 @default.
• W3173883896 cites W2087322129 @default.
• W3173883896 cites W2089432287 @default.
• W3173883896 cites W2090826718 @default.
• W3173883896 cites W2091830940 @default.
• W3173883896 cites W2093660899 @default.
• W3173883896 cites W2100912112 @default.
• W3173883896 cites W2110643873 @default.
• W3173883896 cites W2120290958 @default.
• W3173883896 cites W2129034648 @default.
• W3173883896 cites W2130630814 @default.
• W3173883896 cites W2135998787 @default.
• W3173883896 cites W2136412900 @default.
• W3173883896 cites W2140478861 @default.
• W3173883896 cites W2147084397 @default.
• W3173883896 cites W2148910303 @default.
• W3173883896 cites W2151889253 @default.
• W3173883896 cites W2155758917 @default.
• W3173883896 cites W2161367756 @default.
• W3173883896 cites W2193304014 @default.
• W3173883896 cites W2289296632 @default.
• W3173883896 cites W2293336016 @default.
• W3173883896 cites W2319487633 @default.
• W3173883896 cites W2327587770 @default.
• W3173883896 cites W2336451801 @default.
• W3173883896 cites W2514973692 @default.
• W3173883896 cites W2563548139 @default.
• W3173883896 cites W2584616333 @default.
• W3173883896 cites W2592481914 @default.
• W3173883896 cites W2593467896 @default.
• W3173883896 cites W2892256312 @default.
• W3173883896 cites W2903042106 @default.
• W3173883896 cites W2904042019 @default.
• W3173883896 cites W2946395141 @default.
• W3173883896 cites W2961336705 @default.
• W3173883896 cites W2966604413 @default.
• W3173883896 cites W3002313984 @default.
• W3173883896 cites W3005479091 @default.
• W3173883896 cites W4210979710 @default.
• W3173883896 cites W4244876931 @default.
• W3173883896 doi "https://doi.org/10.1101/2021.06.30.450624" @default.
• W3173883896 hasPublicationYear "2021" @default.
• W3173883896 type Work @default.

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