Calcium Microdomain Formation a t the Perisynaptic Cradle Due to NCX Reversal: A computational study

John Wade, Kevin Breslin, KongFatt Wong-Lin, Jim Harkin, Bronac Flanagan, Harm Van Zalinge, Steve Hall, Mark Dallas, Angela Bithell, Alexei Verkhratsky, LJ McDaid

Research output: Contribution to journalArticle

Abstract

It has recently been proposed using a multi-compartmental mathematical model that negatively fixed charged membrane-associated sites constrain the flow of cations in perisynaptic astroglial processes. This restricted movement of ions between the perisynaptic cradle (PsC), principal astroglial processes and the astrocyte soma gives rise to potassium (K +) and sodium (Na +) microdomains at the PsC. The present paper extends the above model to demonstrate that the formation of an Na + microdomain can reverse the Na +/Ca 2+ exchanger (NCX) thus providing an additional source of calcium (Ca 2+) at the PsC. Results presented clearly show that reversal of the Na +/Ca 2+ exchanger is instigated by a glutamate transporter coupled increase in concentration of cytoplasmic [Na +]i at the PsC, which and instigates Ca 2+ influx through the NCX. As the flow of Ca 2+ along the astrocyte process and away from the PsC is also constrained by Ca 2+ binding proteins, then a Ca 2+ microdomain forms at the PsC. The paper also serves to demonstrate that the EAAT, NKA, and NCX represent the minimal requirement necessary and sufficient for the development of a Ca 2+ microdomain and that these mechanisms directly link neuronal activity and glutamate release to the formation of localized Na + and Ca 2+ microdomains signals at the PsC. This local source of Ca 2+ can provide a previously underexplored form of astroglial Ca 2+ signaling.

LanguageEnglish
Article number185
Pages1-13
Number of pages13
JournalFrontiers in Cellular Neuroscience
Volume13
DOIs
Publication statusPublished - 7 May 2019

Fingerprint

Sodium-Calcium Exchanger
Calcium
Astrocytes
Amino Acid Transport System X-AG
Carisoprodol
Cations
Glutamic Acid
Potassium
Theoretical Models
Sodium
Ions
Membranes

Keywords

  • perisynaptic cradle
  • calcium microdomains
  • Astrocytic process
  • Na+/Ca2+ exchange
  • compartment model
  • Glutamate transport
  • Sodium dynamics
  • Calcium microdomains
  • Perisynaptic cradle
  • Compartment model
  • Na /Ca exchange

Cite this

Wade, John ; Breslin, Kevin ; Wong-Lin, KongFatt ; Harkin, Jim ; Flanagan, Bronac ; Van Zalinge, Harm ; Hall, Steve ; Dallas, Mark ; Bithell, Angela ; Verkhratsky, Alexei ; McDaid, LJ. / Calcium Microdomain Formation a t the Perisynaptic Cradle Due to NCX Reversal : A computational study. 2019 ; Vol. 13. pp. 1-13.
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Calcium Microdomain Formation a t the Perisynaptic Cradle Due to NCX Reversal : A computational study. / Wade, John; Breslin, Kevin; Wong-Lin, KongFatt; Harkin, Jim; Flanagan, Bronac; Van Zalinge, Harm; Hall, Steve; Dallas, Mark; Bithell, Angela; Verkhratsky, Alexei; McDaid, LJ.

Vol. 13, 185, 07.05.2019, p. 1-13.

Research output: Contribution to journalArticle

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AU - Breslin, Kevin

AU - Wong-Lin, KongFatt

AU - Harkin, Jim

AU - Flanagan, Bronac

AU - Van Zalinge, Harm

AU - Hall, Steve

AU - Dallas, Mark

AU - Bithell, Angela

AU - Verkhratsky, Alexei

AU - McDaid, LJ

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