Sodium-Calcium Exchanger Can Account for Regenerative Ca2+ Entry in Thin Astrocyte Processes

Frontiers in Cellular Neuroscience
Alexey R BrazheDmitry E Postnov

Abstract

Calcium transients in thin astrocytic processes can be important in synaptic plasticity, but their mechanism is not completely understood. Clearance of synaptic glutamate leads to increase in astrocytic sodium. This can electrochemically favor the reverse mode of the Na/Ca-exchanger (NCX) and allow calcium into the cell, accounting for activity-dependent calcium transients in perisynaptic astrocytic processes. However, cytosolic sodium and calcium are also allosteric regulators of the NCX, thus adding kinetic constraints on the NCX-mediated fluxes and providing for complexity of the system dynamics. Our modeling indicates that the calcium-dependent activation and also calcium-dependent escape from the sodium-mediated inactive state of the NCX in astrocytes can form a positive feedback loop and lead to regenerative calcium influx. This can result in sodium-dependent amplification of calcium transients from nearby locations or other membrane mechanisms. Prolonged conditions of elevated sodium, for example in ischemia, can also lead to bistability in cytosolic calcium levels, where a delayed transition to the high-calcium state can be triggered by a short calcium transient. These theoretical predictions call for a dedicated experi...Continue Reading

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Citations

Sep 3, 2020·Nature Reviews. Neuroscience·Alexey SemyanovAmit Agarwal
Aug 17, 2019·Glia·Shanshan SongDandan Sun
Nov 17, 2020·Frontiers in Cellular Neuroscience·Jeiwon Cho, Yeowool Huh
Mar 19, 2021·Frontiers in Cellular Neuroscience·László HéjaJulianna Kardos

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