L-type Voltage-gated Calcium Channel Modulators Inhibit Glutamate-induced Morphology in Astrocytoma Cells

ABSTRACT The excitatory neurotransmitter glutamate evokes physiological responses within the astrocytic network that lead to fine morphological dynamics. However, the mechanism by which astrocytes couple glutamate sensing with cellular calcium rise remains unclear. Employing natural properties of U118-MG astrocytoma cells, we tested a possible connection between L-type voltage-gated calcium channels (Ca v ) and glutamate receptors. Using live confocal imaging and pharmacological inhibitors, the extension of U118-MG processes upon glutamate exposure are shown to depend mainly on extracellular calcium entry via L-type Ca v ’s. Inhibitors of the Ca v α1 protein, decreased astrocytic filopodia extension; while, gabapentinoids, ligands of the Ca v ’s α2δ auxiliary subunit blocked all process growth. This study suggests that α2δ is the main contributor to Ca v ’s role in glutamate-dependent filopodiagenesis. It opens new avenues of research on the role of α2δ in neuron-astrocyte glutamate signaling and neurochemical signaling at tripartite synapses.