The effect of lidocaine on cholinergic neurotransmission in an identified reconstructed synapse.

Background: The presynaptic effect of lidocaine on cholinergic synaptic transmission is unclear because of the difficulty in identifying presynaptic neurons and the complexity of the central nervous system in vivo. To clarify the effect of lidocaine on cholinergic synapse, we reconstructed a cultured soma-soma chemical synapse model consisting of two identified visceral dorsal 4 (VD4) and left pedal e-1 (LPeD1) neurons from the snail, Lymnaea stagnalis, in vitro, and used it to determine how lidocaine affects cholinergic synaptic transmission.

Methods: The response to acetylcholine and excitatory postsynaptic potential (EPSP) amplitude was recorded in the reconstructed chemical synaptic transmission model composed of VD4 and LPeD1 neurons. The currents for acetylcholine measurements were made under voltage-clamp in the presynaptic VD4 and postsynaptic LPeD1 neurons.

Results: Lidocaine inhibited both EPSP and the response for acetylcholine of the postsynaptic neuron. EPSP amplitude was reduced in a voltage-dependent manner in the presynaptic neuron, and lidocaine induced a hyperpolarization shift of the voltage-dependent inactivation curves of EPSP amplitude.

Conclusions: Lidocaine inhibits cholinergic synaptic transmission with a voltage-dependent inactivation of EPSP amplitude through the membrane potential depolarization of presynaptic neurons.