MECHANISM OF KETAMINE BLOCK OF NERVE-CONDUCTION

  • 1 January 1977
    • journal article
    • research article
    • Vol. 201  (1) , 162-170
Abstract
The mode of action of ketamine on the nerve membrane was studied in intact and internally perfused squid [Loligo pealii] giant axons at 10-12.degree. C. Voltage clamp techniques were 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, ketamine decreased the resting membrane potential, suppressed steady-state conductances and slightly decreased the leakage conductance, although the last effect was not statistically significant. Peak transient conductance was not appreciably affected. 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 reversal potential for peak transient current towards hyperpolarization. The shift was estimated to be 28.5 mV for 200 .mu.M ketamine. Washing the intact axons with drug-free sea water shifted the reversal potential further towards membrane hyperpolarization. Internal washing quickly returned the reversal potential to near control value. The change in resting Na influx caused by external exposure to ketamine was also measured by using radioactive Na in external sea water at 10.degree. C. Ketamine (200 .mu.M) changed the resting Na influx from (28.9 .+-. 5.6) .times. 10-12 to (41.8 .+-. 5.6) .times. 10-12 mol/cm2-s (mean .+-. S.E.M. [standard error of the mean]). The shift in the reversal potential for peak current caused by ketamine is due partly to Na+ accumulation inside the nerve and partly to the increase in the PK/PNa [K permeability/Na permeability] 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.