Ca2+-permeable AMPA receptors in mouse olfactory bulb astrocytes

Abstract

Ca²⁺ signaling in astrocytes is considered to be mainly mediated by metabotropic receptors linked to intracellular Ca²⁺ release. However, recent studies demonstrate a significant contribution of Ca²⁺ influx to spontaneous and evoked Ca²⁺ signaling in astrocytes, suggesting that Ca²⁺ influx might account for astrocytic Ca²⁺ signaling to a greater extent than previously thought. Here, we investigated AMPA-evoked Ca²⁺ influx into olfactory bulb astrocytes in mouse brain slices using Fluo-4 and GCaMP6s, respectively. Bath application of AMPA evoked Ca²⁺ transients in periglomerular astrocytes that persisted after neuronal transmitter release was inhibited by tetrodotoxin and bafilomycin A1. Withdrawal of external Ca²⁺ suppressed AMPA-evoked Ca²⁺ transients, whereas depletion of Ca²⁺ stores had no effect. Both Ca²⁺ transients and inward currents induced by AMPA receptor activation were partly reduced by Naspm, a blocker of Ca²⁺-permeable AMPA receptors lacking the GluA2 subunit. Antibody staining revealed a strong expression of GluA1 and GluA4 and a weak expression of GluA2 in periglomerular astrocytes. Our results indicate that Naspm-sensitive, Ca²⁺-permeable AMPA receptors contribute to Ca²⁺ signaling in periglomerular astrocytes in the olfactory bulb.