When Na modulates Ca: nonlinear interplay between Na/Ca-exchanger and IP3-mediated Ca oscillations in astrocytes

We present a composite model of astrocytic Ca2+ dynamics, which includes both IP3-mediated release from intracellular Ca2+ stores and bidirectional exchange through the plasma membrane, mediated by the Na+/Ca2+- exchanger (NCX). The NCX kinetic model is formulated in the Hodgkin/Huxley formalism, taking into account the glutamate transporter-mediated increase in Na+ during synaptic activity and Na+- and Ca2+-dependent regulation. We define main dynamic regimes and transitions in a point model, describing dynamics in an individual astrocyte segment. We demonstrate NCX-based modulation of store-mediated calcium oscillations (amplitude, frequency and amplitude-frequency), analyze and compare calcium dynamics in models with and without allosteric regulation of NCX by intracellular ions.

[1]  B. Khakh,et al.  Astrocyte calcium signaling: from observations to functions and the challenges therein. , 2015, Cold Spring Harbor perspectives in biology.

[2]  Vladimir Parpura,et al.  Plasmalemmal Na+/Ca2+ exchanger modulates Ca2+-dependent exocytotic release of glutamate from rat cortical astrocytes , 2012, ASN neuro.

[3]  A. Verkhratsky,et al.  Astroglial calcium signalling in Alzheimer's disease. , 2017, Biochemical and biophysical research communications.

[4]  Andrey Yu. Verisokin,et al.  Raindrops of synaptic noise on dual excitability landscape: an approach to astrocyte network modelling , 2018, Saratov Fall Meeting.

[5]  Mayeul Collot,et al.  Calcium dynamics in astrocyte processes during neurovascular coupling , 2014, Nature Neuroscience.

[6]  Stephen J. Smith,et al.  Neuronal activity triggers calcium waves in hippocampal astrocyte networks , 1992, Neuron.

[7]  Terrence J. Sejnowski,et al.  Astrocytes contribute to gamma oscillations and recognition memory , 2014, Proceedings of the National Academy of Sciences.

[8]  N. Brunel,et al.  Astrocytes: Orchestrating synaptic plasticity? , 2015, Neuroscience.

[9]  Christopher R. Weber,et al.  Cardiac Na+–Ca2+ exchanger: dynamics of Ca2+‐dependent activation and deactivation in intact myocytes , 2013, The Journal of physiology.

[10]  Alexey Semyanov Spatiotemporal pattern of calcium activity in astrocytic network. , 2019, Cell calcium.

[11]  D. Postnov,et al.  Sodium–Calcium Exchanger Can Account for Regenerative Ca2+ Entry in Thin Astrocyte Processes , 2018, Front. Cell. Neurosci..

[12]  P. Haydon Glia: listening and talking to the synapse , 2001, Nature Reviews Neuroscience.

[13]  O. Sosnovtseva,et al.  Astrocyte calcium signaling: Interplay between structural and dynamical patterns. , 2018, Chaos.

[14]  Donald M. Bers,et al.  Allosteric Regulation of Na/Ca Exchange Current by Cytosolic Ca in Intact Cardiac Myocytes , 2001, The Journal of general physiology.

[15]  Ghanim Ullah,et al.  Anti-phase calcium oscillations in astrocytes via inositol (1, 4, 5)-trisphosphate regeneration. , 2006, Cell calcium.

[16]  J. Rinzel,et al.  Equations for InsP3 receptor-mediated [Ca2+]i oscillations derived from a detailed kinetic model: a Hodgkin-Huxley like formalism. , 1994, Journal of theoretical biology.

[17]  A. Verkhratsky,et al.  Sodium dynamics: another key to astroglial excitability? , 2012, Trends in Neurosciences.

[18]  E. Ben-Jacob,et al.  Glutamate regulation of calcium and IP3 oscillating and pulsating dynamics in astrocytes , 2009, Journal of biological physics.

[19]  R. Dipolo,et al.  Na+ entry via glutamate transporter activates the reverse Na+/Ca2+ exchange and triggers ‐induced Ca2+ release in rat cerebellar Type‐1 astrocytes , 2007, Journal of neurochemistry.