The perisynaptic Schwann cells are intimately integrated into the majority of vertebrate neuromuscular junctions. The processes of perisynaptic Schwann cells are closely associated with nerve terminals and send finger-like extensions directly into the synaptic cleft where they terminate very closely to the active zones. Similar to astrocytes, perisynaptic Schwann cells utilize intracellular Ca2+ as the substrate of their excitation. High-frequency stimulation of nerve terminals triggers [Ca2+]i elevation in neighbouring Schwann cells. These [Ca2+]i responses are mediated by neurotransmitters, as perisynaptic Schwann cells are endowed with metabotropic acetylcholine, ATP and substance P receptors, linked to Ca2+ release from the ER via the InsP3 second messenger system. The Ca2+ signals generated in Schwann cells underlie the feedback to the neuronal terminal, as they can either potentiate or depress the release of neurotransmitters from the latter. The net effect (potentiation vs. depression) seems to be regulated by the frequency of synaptic activation.
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