Translating from Na+ to Ca2+: Na/Ca-exchanger exerts Na+-dependent control over astrocytic Ca2+ oscillations

Recently accumulated evidences suggest that astrocyte signaling is in touch link with extracellular volume regulation and interstitial fluid drainage from the brain. Classical understanding of astrocyte activity is based on IP3-dependent calcium exchange with intracellular stores. Recent evidence shifts focus to calcium entry from extracellular space via multiple mechanisms and widens it to taking other ions into account. It has been hypothesized that Na/Ca-exchanger can translate activity-dependent Na+ transients into modulation of Ca2+ dynamics. We combine a model of IP3-based Ca2+ dynamics with a model of Ca2+ flow through Na/Ca-exchanger to provide theoretical insights into the possible effects of such modulation. We find that the exchanger can provide for bidirectional Na+-dependent modulation of the sensitivity to extracellular glutamate, oscillation amplitude and frequency modulation, as well as extending the available set of dynamical regimes. The extent of the emergent Na+ sensitivity is predicted to be scaled by a morphology-dependent balance between the maximal flow through the exchanger and the rate of entry from intracellular stores.