AMPA Receptor-Mediated Ca²⁺ Transients in Mouse Olfactory Ensheathing Cells

Ca²⁺ signaling in glial cells is primarily triggered by metabotropic pathways and the subsequent Ca²⁺ release from internal Ca²⁺ stores. However, there is upcoming evidence that various ion channels might also initiate Ca²⁺ rises in glial cells by Ca²⁺ influx. We investigated AMPA receptor-mediated inward currents and Ca²⁺ transients in olfactory ensheathing cells (OECs), a specialized glial cell population in the olfactory bulb (OB), using whole-cell voltage-clamp recordings and confocal Ca²⁺ imaging. By immunohistochemistry we showed immunoreactivity to the AMPA receptor subunits GluA1, GluA2 and GluA4 in OECs, suggesting the presence of AMPA receptors in OECs. Kainate-induced inward currents were mediated exclusively by AMPA receptors, as they were sensitive to the specific AMPA receptor antagonist, GYKI53655. Moreover, kainate-induced inward currents were reduced by the selective Ca²⁺-permeable AMPA receptor inhibitor, NASPM, suggesting the presence of functional Ca²⁺-permeable AMPA receptors in OECs. Additionally, kainate application evoked Ca²⁺ transients in OECs which were abolished in the absence of extracellular Ca²⁺, indicating that Ca²⁺ influx via Ca²⁺-permeable AMPA receptors contribute to kainate-induced Ca²⁺ transients. However, kainate-induced Ca²⁺ transients were partly reduced upon Ca²⁺ store depletion, leading to the conclusion that Ca²⁺ influx via AMPA receptor channels is essential to trigger Ca²⁺ transients in OECs, whereas Ca²⁺ release from internal stores contributes in part to the kainate-evoked Ca²⁺ response. Endogenous glutamate release by OSN axons initiated Ca²⁺ transients in OECs, equally mediated by metabotropic receptors (glutamatergic and purinergic) and AMPA receptors, suggesting a prominent role for AMPA receptor mediated Ca²⁺ signaling in axon-OEC communication.