Computational modeling predicts ephemeral acidic microdomains in the 
glutamatergic synaptic cleft

Feghhi, Touhid; Hernandez, Roberto X.; Stawarski, Michal; Thomas, Connon I.; Kamasawa, Naomi; Lau, A. W. C.; Macleod, Gregory T.

Computational modeling predicts ephemeral acidic microdomains in the glutamatergic synaptic cleft

Feghhi, T., Hernandez, R. X., Stawarski, M., Thomas, C. I., Kamasawa, N., Lau, A. W. C., & Macleod, G. T. (2021). Computational modeling predicts ephemeral acidic microdomains in the glutamatergic synaptic cleft. Biophysical Journal, (24), 5575-5591. Retrieved from https://www.sciencedirect.com/science/article/pii/S0006349521009589.

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アイテムのパーマリンク: https://hdl.handle.net/21.11116/0000-000C-DFAE-6 版のパーマリンク: https://hdl.handle.net/21.11116/0000-000C-DFAF-5

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その他のタイトル : Biophysical Journal

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Feghhi, Touhid, 著者
Hernandez, Roberto X., 著者
Stawarski, Michal, 著者
Thomas, Connon I.¹, 著者
Kamasawa, Naomi¹, 著者
Lau, A. W. C., 著者
Macleod, Gregory T., 著者

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1Max Planck Florida Institute for Neuroscience, Max Planck Society, One Max Planck Way, Jupiter FL 33458, USA, ou_1950288

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要旨: 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.

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日付: 出版: 2021

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識別子（DOI, ISBNなど）: URI: https://www.sciencedirect.com/science/article/pii/S0006349521009589
URI: https://www.sciencedirect.com/science/article/pii/S0006349521009589/pdfft?md5=b5ab81c013c0f57d48747755cbff2700&pid=1-s2.0-S0006349521009589-main.pdf&isDTMRedir=Y

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出版物名: Biophysical Journal

出版物の別名 : Biophysical Journal

種別: 学術雑誌

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ページ: - 巻号: (24) 通巻号: - 開始・終了ページ: 5575 - 5591 識別子（ISBN, ISSN, DOIなど）: ISBN: 0006-3495

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