Actions of ketamine on synaptic transmission in frog sympathetic ganglia.

The effects of ketamine, a clinically used general anaesthetic, on isolated paravertebral sympathetic ganglia were investigated with extracellular and intracellular techniques. Ketamine, in concentrations of 10^?5M–10^?3M, reversibly blocked orthodromically induced action potentials. In concentrations which completely abolished the nicotinic response, ketamine did not entirely depress the muscarinic and noncholinergic components of ganglionic transmission. Ketamine depressed the postsynaptic membrane sensitivity to acetylcholine which was determined by comparing the responses to iontophoretically applied acetylcholine before and after ketamine. Concentrations of ketamine less than 10^?3M, which effectively blocked ganglionic transmission, did not significantly alter the passive membrane properties of the postsynaptic membrane. At 10^?3M, ketamine acted to simultaneously depolarize the postsynaptic membrane and increase the effective membrane resistance by decreasing the membrane conductance to potassium. In concentrations greater than 10^?3M, ketamine acted non-selectively to block reversibly the nicotinic, muscarinic and non-cholinergic ganglionic responses. These results demonstrate that ketamine. in addition to its strong central action, also has a direct depressant action upon peripheral synaptic transmission.