AMPA Receptor-Mediated Ca(2+) Transients in Mouse Olfactory Ensheathing Cells

Ca(2+) signaling in glial cells is primarily triggered by metabotropic pathways and the subsequent Ca(2+) release from internal Ca(2+) stores. However, there is upcoming evidence that various ion channels might also initiate Ca(2+) rises in glial cells by Ca(2+) influx. We investigated AMPA receptor-mediated inward currents and Ca(2+) transients in olfactory ensheathing cells (OECs), a specialized glial cell population in the olfactory bulb (OB), using whole-cell voltage-clamp recordings and confocal Ca(2+) 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 Ca(2+)-permeable AMPA receptor inhibitor, NASPM, suggesting the presence of functional Ca(2+)-permeable AMPA receptors in OECs. Additionally, kainate application evoked Ca(2+) transients in OECs which were abolished in the absence of extracellular Ca(2+), indicating that Ca(2+) influx via Ca(2+)-permeable AMPA receptors contribute to kainate-induced Ca(2+) transients. However, kainate-induced Ca(2+) transients were partly reduced upon Ca(2+) store depletion, leading to the conclusion that Ca(2+) influx via AMPA receptor channels is essential to trigger Ca(2+) transients in OECs, whereas Ca(2+) release from internal stores contributes in part to the kainate-evoked Ca(2+) response. Endogenous glutamate release by OSN axons initiated Ca(2+) transients in OECs, equally mediated by metabotropic receptors (glutamatergic and purinergic) and AMPA receptors, suggesting a prominent role for AMPA receptor mediated Ca(2+) signaling in axon-OEC communication.