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 (Cav) 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 Cavs. Inhibitors of the Cav 1 protein, decreased astrocytic filopodia extension; while, gabapentinoids, ligands of the Cavs 2{delta} auxiliary subunit blocked all process growth. This study suggests that 2{delta} is the main contributor to Cavs role in glutamate-dependent filopodiagenesis. It opens new avenues of research on the role of 2{delta} in neuron-astrocyte glutamate signaling and neurochemical signaling at tripartite synapses.