AbstractThe effects on excitation contraction coupling (ECC) of ketamine (a dissociative general anesthetic) were investigated using the sartorius muscle of the frog. Extracellular studies revealed that ketamine depressed action potential production in a concentration‐dependent manner. Ketamine decreased both the conduction velocity and the compound action potential while concomitantly increasing the threshold current. Intracellular studies showed that ketamine caused a slight non‐significant decrease in the membrane potential and also decreased the threshold potential (mechanical threshold). Ketamine (1.5 × 10−4M and 3.0 × 10−4M) initially potentiated and then blocked the twitch response elicited by direct muscle stimulation. Both of these effects were statistically different from control values. These findings suggest that ketamine alters action potential production in frog skeletal muscle. This property of ketamine contributes in part to the disruption of ECC observed with this drug. The results suggest that ketamine probably interferes with calcium binding, its release and/or its fluxes which may contribute to the initial potentiation and subsequent depression of twitc