Mechanism of ketamine block of nerve conduction

BB Shrivastav

The node of action of ketamine on the nerve membrane has been studied in intact and internally perfused squid giant axons at 10-12 degrees C. Voltage clamp techniques have been employed to measure the maximal values of peak transient and steady-state conductances as an index of activity and to measure the apparent reversal potential for peak transient current. When applied externally to intact axons, kketamine decreased the resting membrane potential, suppressed steady-state conductances and slightly decreased theleakage conductance, although the last effect was not statistically significant. Peak transient conductance was not appreciably affected. However, when the drug was applied internally, both peak transient and steady-state conductances were suppressed. Ketamine applied externally either to intact axons or to internally perfused axons with internal flow temporarily suspended shifted the apparent reversalpotential for peak transient current towards hyperpolarization. The shift was estimated to be 28.5 mV for 200 micronM ketamine. Wahing the intact axons with drug-free sea water shifted the reversal potential further towards membrane hyperploarization. However, internal washing quickly returned the reversal potential to near control value. The change in resting sodium influx caused by external exposure to ketamine was also measured by using radioactive sodium in external sea water at 10 degrees C. Ketamine (200 micronM) changed the resting sodium influx from (28.9 +/- 5.6) x 10(-12 mol/cm2-sec to (41.8 +/- 5.6) x 10(-12 mol/cm2-sec (mean +/- S.E.M.). The data presented in this paper strongly suggest that the shift in the reversal potential for peak current caused by ketamine is due partly to sodium ion accumulation inside the nerve and partly to the increase in the PR/PNa ratio during peak current. These changes would have a profound narcotic effect on the electrical activity of nerve fibers and nerve endings in the brain during ketamine anesthesia.

Volume 201, Issue 1, pp. 162-170, 04/01/1977
Copyright © 1977 by American Society for Pharmacology and Experimental Therapeutics

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