Lidocaine increases intracellular sodium concentration through voltage-dependent sodium channels in an identified Lymnaea neuron

Abstract

Background: The local anesthetic lidocaine affects neuronal excitability in the central nervous system; however, the mechanisms of such action remain unclear. The intracellular sodium concentration ([Na +] i) and sodium currents (INa) are related to membrane potential and excitability. Using an identifiable respiratory pacemaker neuron from Lymnaea stagnalis, the authors sought to determine whether lidocaine changes [Na +] i and membrane potential and whether INa is related to these changes. Methods: Intracellular recording and sodium imaging were used simultaneously to measure membrane potentials and [Na +] i, respectively. Measurements for [Na +] i were made in normal, high-Na +, and Na +-free salines, with membrane hyperpolarization, and with tetrodotoxin pretreatment trials. Furthermore, changes of INa were measured by whole cell patch clamp configuration. Results: Lidocaine increased [Na +] i in a dose-dependent manner concurrent with a depolarization of the membrane potential. In the presence of high-Na + saline, [Na +] i increased and the membrane potential was depolarized; the addition of lidocaine further increased [Na +] i, and the membrane potential was further depolarized. In Na +-free saline or in the presence of tetrodotoxin, lidocaine did not change [Na +] i. Similarly, hyperpolarization of the membrane by current injections also prevented the lidocaine-induced increase of [Na +] i. In the patch clamp configuration, membrane depolarization by lidocaine led to an inward sodium influx. A persistent reduction in membrane potential, resulting from lidocaine, brings the cell within the window current of INa where sodium channel activation occurs. Conclusion: Lidocaine increases intracellular sodium concentration and promotes excitation through voltage-dependent sodium channels by altering membrane potential in the respiratory pacemaker neuron.