Neural electrical activity has opposing effects on the development of oligoden-drocytes and Schwann cells. In the PNS, electrical activity inhibits myelination, by down-regulation of L1 and by the release of ATP to act on P2Y receptors on Schwann cells and inhibit their proliferation, differentiation and myelination. Electrical activity has the opposite effect in the CNS. Blocking (tetrodotoxin) or increasing (alpha-scorpion toxin) neuronal electrical activity respectively inhibit and promote myelination. These effects are mediated by adenosine and ATP released by electrically active axons. Adenosine acts on OPCs, which express A1 receptors, as a potent inhibitor of proliferation, and stimulates their differentiation. ATP acts on astrocytes to trigger them to release leukaemia inhibitory factor (LIF), which in turn acts on oligodendrocytes to promote myelination. The opposing actions of ATP and adenosine on differentiation of Schwann cells and oligo-dendrocytes provide an explanation for the opposite effects of impulse activity on myelination in the CNS and PNS. In the CNS, glutamate acting on AMPA receptors inhibits OPC proliferation and differentiation, by cell depolarization and blockade of voltage-dependent K+ channels. It has not been shown whether this is related to neuronal activity.
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