Abstract
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.
Highlights
Ca2+ signaling in glial cells is involved in various intercellular processes such as the release of gliotransmitters, modulation of synaptic transmission, long-range Ca2+ wave propagation, and neurovascular coupling (Haydon, 2001; Carmignoto and Gomez-Gonzalo, 2010)
GluA2-lacking AMPA receptors show a high permeability for Ca2+ whereas GluA2-containing AMPA receptors are impermeable for Ca2+ (Hollmann et al, 1991)
We investigated the role of AMPA receptors in Olfactory ensheathing cells (OECs) physiology and axon-OEC communication
Summary
Ca2+ signaling in glial cells is involved in various intercellular processes such as the release of gliotransmitters, modulation of synaptic transmission, long-range Ca2+ wave propagation, and neurovascular coupling (Haydon, 2001; Carmignoto and Gomez-Gonzalo, 2010). Storeoperated channels as well as transient receptor potential (TRP) channels contribute to Ca2+ signaling in astrocytes (Singaravelu et al, 2006; Rungta et al, 2016; Belkacemi et al, 2017; Rakers et al, 2017; Toth et al, 2019) These studies indicate that Ca2+ influx might play a previously underestimated role in glial cell physiology and function. Olfactory ensheathing cells (OECs) represent a specialized population of glial cells, exclusively located in the olfactory nerve layer (ONL) in the olfactory bulb (OB) and the peripheral olfactory mucosa (Su and He, 2010; Lohr et al, 2014) They support growth and guidance of axons of olfactory sensory neurons (OSN) from the olfactory epithelium (OE) into the main OB (Graziadei and Graziadei, 1979; Doucette, 1984; Yang et al, 2015). Electrical stimulation of OSN axons evoked Ca2+ transients mediated by metabotropic receptors as well as Ca2+-permeable AMPA receptors, suggesting a role for AMPA receptor-mediated Ca2+ signaling in axon-OEC communication
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