Figure 1. Astrocyte-neuron relationships.

Astrocytes are involved in the uptake and release of neurotransmitters, trophic factors and energy substrates for neurons and in the control of ion homeostasis. Astrocytes respond with Ca²⁺ elevations to neurotransmitters released during synaptic activity and, in turn, control neuronal excitability and synaptic transmission through the Ca2⁺-dependent release of gliotransmitters such as glutamate, ATP, GABA and D-serine. The uptake of the neurotransmitter glutamate from the synaptic cleft by astrocytes occurs via Na⁺-dependent excitatory amino acid transporters (EAATs). Glutamate is then converted into glutamine by glutamine synthetase (GS) and released back to neurons where it is converted to glutamate by glutaminase. Na⁺, K⁺-ATPase provides the Na⁺-mediated driving force for glutamate uptake. Trophic factors like BDNF, GDNF, NGF, IGF and thrombospondin, produced and released by astrocytes regulate synapse formation, maintenance and remodelling. Glutamatergic activation induces lactate release from astrocytes via monocarboxylate transporters (MCT). Astrocytes also control water and ion exchange in the synaptic cleft through water (AQP4) and ion (Kir4.1) channels and ion exchangers (Na⁺/H⁺ exchanger, Na⁺/Ca⁺² exchanger). Kir4.1 is the main channel involved in potassium buffering in astrocytes. K⁺ ions travel through the astrocyte syncytium via gap junctions or are siphoned in the blood circulation. Carbonic anhydrase (CA) in astrocytes converts CO₂ into H⁺ and HCO³⁻. Two HCO³⁻ are transported into the extracellular space along with one Na⁺ via the Na⁺-HCO³⁻ co-transporter (NBC), thereby increasing the extracellular ion buffering power. Excess H⁺ in neurons is extruded via the Na⁺/H⁺ exchanger (NHE).