High affinity glutamate transporters are expressed in Schwann cells and regulated by allopregnanolone

Abstract

Aim: L-Glutamate, the major excitatory neurotransmitter in the central nervous system (CNS), is implicated in several neurological disorders including peripheral neuropathies (Watkins, 2000). Among therapeutic approaches for treating these diseases, it is considered the block of glutamate receptors with small antagonist molecules. Alternative therapeutic targets are the Na+-dependent high affinity glutamate transporters, the main regulators of extracellular glutamate. Recently, glutamate transporters were identified in vivo in the peripheral nervous system (PNS), whereas their cellular location has not been investigated. Our results give a complete characterization of the glutamate transporters system in the Schwann cell cultures, the myelin forming cells in the PNS. Methods: We observed that Schwann cells expressed EAAC1 and GLAST in the plasma membrane as well as in intracellular vesicular compartments. Results: Uptake experiments confirmed that these transporters were present and functional in Schwann cells and that their activity was modulated by exposure to allopregnanolone 10 nM (progesterone's metabolite). Up-regulation by allopregnanolone did not require protein's neosynthesis and was prevented by actin depolimerization. Conclusion: Studies are in progress in order to verify whether the transport up-regulation relies on allosteric modulation or changes in the surface density of glutamate transporters, via redistribution from intracellular compartments to the plasma membrane