Current-clamp analysis of a time-dependent rectification in rat optic nerve.

1. Rat optic nerves were studied using intra-axonal and whole-nerve recording techniques in a sucrose-gap chamber. Constant-current pulses were applied across the outer compartments of the chamber to achieve a current clamp. 2. The nerves displayed a prominent time-dependent conductance increase elicited by a hyperpolarizing constant-current pulse, as evidenced by a relaxation or 'sag' in membrane potential towards resting potential. The inward current began at about 80 ms and reached a steady level over the next 100-200 ms. Its magnitude progressively increased with increasing levels of hyperpolarization. 3. The inward current elicited by hyperpolarization was reduced, but not abolished, when Na+ was reduced from the normal bath concentration of 151 mM to 0 mM. In Na(+)-free solutions the bath K+ concentration, [K+]o, was varied between 0 and 5 mM; the inward current was greatest when [K+]o was 5 mM and was abolished when [K+]o was zero. 4. The inward current was not abolished by tetrodotoxin (TTX), tetraethylammonium (TEA) or 4-aminopyridine (4-AP) suggesting that conventional voltage-dependent sodium and potassium channels do not underlie the time-dependent conductance increase. Low concentrations of Cs+ completely blocked the inward current, and Ba2+ induced a partial block. External application of divalent cations (Cd2+ and Mg2+) did not block the inward current. These properties are similar to the inwardly rectifying conductance observed in a central nervous system neurone. 5. Stimulus-response curves obtained during the hyperpolarization pulse, before and during the conductance increase, indicate that excitability is increased during the conductance increase. This along with the intra-axonal recordings demonstrates that the origin of the increased conductance is axonal and not glial. 6. It is concluded that central nervous system myelinated fibres in rat optic nerve display a prominent time-dependent conductance increase in response to hyperpolarization that depends on both Na+ and K+ and is blocked by Cs+. This conductance is similar to an inward rectifier described for a variety of neurone types. The increased axonal excitability observed during the conductance increase suggests that its functional role may be to maintain or stabilize axonal excitability during periods of intense action potential activity.