Electrophysiological studies of the action of ketamine in frog skeletal muscle

Abstract

The effects of the dissociative analgesic anaesthetic, ketamine, on action potential production in frog sartorius muscle fibres, were studied with bipolar extracellular electrodes and intracellular microelectrode techniques. All concentrations of ketamine depressed the extracellularly recorded compound action potential. Low concentrations of ketamine (less than 1 × 10 −4 m) increased excitability by reducing the current needed to initiate an action potential. Higher concentrations of ketamine decreased excitability by inhibiting the maximum rate of rise, the overshoot, and the maximum amplitude of the action potential. The resting membrane potential was not significantly affected by any of the ketamine concentrations employed. The depressant effects of ketamine on the action potential were antagonized in an apparently competitive manner by sodium ions. Ketamine caused a shift in the relationship between rate of fall and amplitude to higher action potential amplitudes, indicating that the drug inhibited the increase in potassium conductance (gK) associated with the falling phase of the action potential. It can be concluded that ketamine decreases excitability in frog sartorius muscle by inhibiting the specific increase in sodium conductance, which normally follows a threshold stimulus and is responsible for the rising phase of the action potential.