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The effects of eserine and D-tubocurarine on the axon and Schwann cell membrane potentials have been studied in the giant nerve fibre of the squid.

1. The addition of eserine at concentrations of up to 10^-4 M to the external sea-water medium has no appreciable effects on either the Schwann cell electrical potential of unstimulated nerve fibres or on the resting and action potentials of the axon.

2. However, eserine at a concentration of 10^-9 M prolongs the long-lasting Schwann cell hyperpolarizations which follow the conduction of impulse trains by the axon.

3. Higher concentrations of eserine (10^-7, 10^-4 M) decrease and block the long-lasting effects of nerve impulse train conduction.

4. D-tubocurarine at concentrations of up to 10^-5 M has no appreciable effect on the resting and action potentials of the axon.

5. However, D-tubocurarine at a concentration of 10^-9 M blocks completely the hyperpolarizing effects of nerve impulse trains on the Schwann cell electrical potential.

6. In addition to its blocking action, D-tubocurarine induces transient hyperpolarizations in the Schwann cells of unstimulated nerve fibres both in intact fibres and in slitted preparations.

7. These findings suggest that a cholinergic system, which may be located at the axon-Schwann cell boundary, is involved in the genesis of the long-lasting Schwann cell hyperpolarization caused by the conduction of nerve impulse trains by the axon.