Time courses of lidocaine effects on sodium membrane currents in small and large neurons.

Time courses of effects of lidocaine on sodium currents and sodium dependent action potentials were studied in somata of small and large neurons. Cultured rat sensory spinal ganglion cells (diameter: 30 microns) and neurons of the buccal ganglion of Helix pomatia (diameter: 150 microns) served as the test cells. The latency of the suppressive action of lidocaine was the longer the larger the of the cells was. Maximal blocking effects occurred within 10 min in sensory spinal ganglion cells and within 40 min in snail neurons. Model calculations based on the assumptions (i) that lidocaine is distributed in the extra- and intracellular space by simple diffusion and (ii) that the drug concentration at the outer surface of the cells is elevated stepwisely, revealed a strong dependency of intracellular concentration changes on the size of the cells. From these findings it is concluded that lidocaine blocks sodium channels primarily from the intracellular side.