Ampa/kainate receptor activation in murine oligodendrocyte precursor cells leads to activation of a cation conductance, calcium influx and blockade of delayed rectifying K⁺ channels

Abstract

Studies during the last few years have shown that glial cells can express a large repertoire of neurotransmitter receptors. In this study, we have characterized the properties of a glutamate receptor in oligodendrocytes and their precursor cells from cultures of mouse brain, using the patch-clamp technique to measure ligand-activated currents and a fura-2 imaging system to determine changes in free cytosolic Ca²⁺ concentration ([Ca²⁺]_i). The precursor cells were identified by their characteristic morphology and their voltage-gated currents as described previously [Sontheimer H.et al. (1989) Neuron 2, 1135–1145]. The ligands kainate, domoate and α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA), as well asl-glutamate but nottrans-1-amino-1,3-cyclopentanedicarboxylate elicited inward currents at a holding potential of − 70 mV and the antagonist 6-cyano-7-nitroquinoxaline-2,3-dione blocked the glutamate- and kainate-induced response reversibly, indicating the expression of an AMPA/kainate-type glutamate receptor. The response is due to the activation of a cationic conductance as revealed by analysing the reversal potential of the kainate-activated current. Receptor activation is accompanied by two additional responses: (i) an increase in [Ca²⁺]_i mediated by depolarization and a subsequent activation of voltage-gated Ca²⁺ channels and (ii) a transient blockade of a delayed rectifying K⁺ current, but not of the A-type K⁺ current. The blockade of the K⁺ current was not due to the increase in [Ca²⁺]_i since it was also observed in Ca²⁺-free bathing solution when no increase in [Ca²⁺]_i was detectable after exposure to kainate. In contrast to precursor cells, oligodendrocytes responded weakly or not at all to glutamate or related ligands.

We conclude that glutamate activates a complex pattern of physiological events in the glial precursor cells, which may play a role during the differentiation process of these cells.