Glutamate activates AMPA receptor conductance in the developing Schwann cells of the mammalian peripheral nerves

Schwann cells (SCs) are myelinating cells of the peripheral nervous system. Although SCs are known to express different channels and receptors on their surface, little is known about the activation and function of these proteins. Ionotropic glutamate receptors are thought to play an essential role during development of SC lineage and during peripheral nerve injury and therefore we sought to study their functional properties. We established a novel preparation of living peripheral nerve slices with preserved cellular architecture, and used a patch-clamp technique to study α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic-acid (AMPA)-receptor-mediated currents in SCs for the first time. We found that the majority of SCs in the nerves dissected from embryonic and neonatal mice of both sexes respond to the application of glutamate with inward current mediated by Ca 2+ -permeable AMPA receptors (AMPARs). Using stationary fluctuation analysis we demonstrate that single-channel conductance of AMPARs in SCs is 8-11 pS which is comparable to neurons. We further show that when SCs become myelinating, they downregulate functional AMPARs. This study is the first to demonstrate AMPAR-mediated conductance in SCs of vertebrates, to investigate elementary properties of AMPARs in these cells, and to provide detailed electrophysiological and morphological characterisation of SCs at different stages of development. SIGNIFICANCE STATEMENT We provide several important conceptual and technical advances in the research of the peripheral nervous system (PNS). We pioneer the first description of AMPA receptor mediated currents in the PNS glia of vertebrates and provide new insights into the properties of AMPA receptor channels in peripheral glia, e.g. their Ca 2+ permeability and single-channel conductance. We describe for the first time, the electrophysiological and morphological properties of Schwann cells (SCs) at different stages of development and show that functional AMPA receptors are expressed only in developing but not in mature SCs. Finally, we introduce a preparation of peripheral nerve slices for patch-clamp recordings. This preparation opens new possibilities for studying the physiology of SCs in animal models and in surgical human samples.