Lidocaine Increases Intracellular Sodium Concentration through Voltage-dependent Sodium Channels in an Identified Lymnaea Neuron

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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.

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