Lidocaine increases intracellular sodium concentration through voltage-dependent sodium channels in an identified lymnaea neuron
Onizuka, S.; Kasaba, T.; Hamakawa, T.; Ibusuki, S.; Takasaki, M.
Anesthesiology 101(1): 110-120
2004
ISSN/ISBN: 0003-3022 PMID: 15220779 Document Number: 571329
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+), 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.