• Shin Onizuka, Toshiharu Kasaba, Toshiro Hamakawa, Shoichiro Ibusuki, and Mayumi Takasaki.
• Department of Anesthesiology, Miyazaki Medical College, University of Miyazaki, Japan. onizuka@shaw.ca
• Anesthesiology. 2004 Jul 1;101(1):110-20.

BackgroundThe 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.MethodsIntracellular 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.ResultsLidocaine 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.ConclusionLidocaine 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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