Axon-glia interactions modulate axonal excitability in mammalian unmyelinated nerves.

A period of electrical activity in unmyelinated nerve fibers is followed by a post-tetanic hyperpolarization (PTH), generated by the hyperactivity of the electrogenic Na(+)-K(+) pump. In order to protect the membrane potential against these strong hyperpolarizations, different types of axonal inward currents are activated during the PTH. We investigated in the rabbit vagus nerve one of these currents, which was activated by carbamylcholine (CCh). We observed that the effect of CCh on the PTH amplitude could be blocked or reversed with scopolamine. Moreover, the PTH amplitude increased when scopolamine alone was added to the perfusate, indicating that an endogenous muscarinic agonist was liberated in the preparation during the period of electrical activity. This CCh-activated current was TEA but not Ba(2+) or Cs(+) sensitive. It has been shown previously that muscarinic acetylcholine receptors (mAChRs) in the rabbit vagus nerve are located on the axonal but not glial membrane and that Schwann cells express several types of purinergic receptors, which activation evoke Ca(2+) transients in Schwann cells. We hypothesise that during electrical activity axons release a transmitter, presumably ATP. This transmitter evoke in the neighbouring Schwann cells a Ca(2+)-dependent liberation of a endogenous muscarinic agonist, which in turn activates a TEA-sensitive inward current in axons. We suggest that the major purpose of this mechanism is the control of the membrane potential during and after a period of intense electrical activity when the Na(+)-K(+) pump generates a robust PTH.