Mechanism of Action of Local Anesthetics on Synaptic Transmission in the Rat

Abstract

The mechanism of action of local anesthetics on synaptic transmission and their effects on synaptic components and on electrophysiologic properties of the nerve cell body are not clear. Therefore, the effects of lidocaine and bupivacaine on pre- and postsynaptic mechanisms underlying synaptic transmission in sympathetic ganglia were studied utilizing the techniques of intracellular recording and stimulation on isolated superfused superior cervical ganglia of rats. Lidocaine and bupivacaine either depressed or completely blocked synaptic transmission in sympathetic ganglia in a dose-dependent manner. Blockade of axonal conduction in presynaptic fibers was preceded by increased latency (the latency increased from 11.2 +/- 0.9 to 16.5 +/- 1.4 ms, mean +/- SEM, P less than 0.01) when the drugs were applied to the presynaptic nerves. Application of the drugs directly to the ganglion produced alterations in postsynaptic membrane properties consisting of decreased membrane resistance (from 40 +/- 3 to 32 +/- 3 M omega, P less than 0.01), increased firing threshold (from 14 +/- 0.5 to 18 +/- 0.5 mV, P less than 0.01), and decreased action potential amplitude (P less than 0.01) and/or blockade of action potential generation. Resting postsynaptic membrane potential did not change significantly. These changes were reversible. However, even after the excitatory postsynaptic potential resulting from presynaptic nerve stimulation had fully recovered during washout of the local anesthetic, the threshold for evoking the spike potential (firing level) still remained elevated for both presynaptic and intracellular stimulation of the ganglion cell, suggesting prolonged cell depression.(ABSTRACT TRUNCATED AT 250 WORDS)