Functional Ca

Glutamate is the main excitatory neurotransmitter in the brain, acting through ionotropic receptors such as AMPA receptors (AMPARs). While their neuronal role is well established, AMPAR function in astrocytes remains poorly understood, especially in the hippocampus. In this study, we investigated the expression and functional properties of astrocytic AMPARs, focusing on their capacity to mediate calcium signaling and inter-cellular communication. Using astrocyte primary cultures, we confirmed the expression of GluA1 and GluA2 subunits, along with detectable levels of GluA4. Calcium imaging revealed that pharmacological AMPAR stimulation elicited intracellular Ca²⁺ signals in a subset of astrocytes which were markedly potentiated when desensitization was impaired. Notably, some of these responses persisted without extracellular Na⁺, compatible with the presence of functional calcium-permeable AMPARs (CP-AMPARs) in hippocampal astrocytes. However, sodium was required for full amplification of the Ca²⁺ signals, suggesting a synergistic role of Na⁺ and Ca²⁺ influx. Pharmacological inhibition of GluA2-lacking AMPARs reduced the responses, supporting the coexistence of GluA2-lacking and GluA2-containing subtypes. Sniffer-calcium assays suggested that strong AMPAR stimulation can engage ATP-dependent signaling, facilitating calcium wave propagation. Altogether, our results reveal functional and heterogeneous AMPAR populations in hippocampal astrocytes. Further investigations will elucidate their physiological roles, localization, and contribution to neuroglial interactions under physiological and pathological conditions.