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Anesth Analg 2005;100:175-182
© 2005 International Anesthesia Research Society
doi: 10.1213/01.ANE.0000139307.91617.6D


PAIN MEDICINE

Lidocaine Excites Both Pre- and Postsynaptic Neurons of Reconstructed Respiratory Pattern Generator in Lymnaea stagnalis

Shin Onizuka, MD, Toshiharu Kasaba, MD, Toshiro Hamakawa, MD, and Mayumi Takasaki, MD

Department of Anesthesiology, Miyazaki Medical College, University of Miyazaki, Kiyotake-Cho, Miyazaki, Japan

Address correspondence and reprint requests to Shin Onizuka, MD, Department of Anesthesiology, Miyazaki Medical College, Kiyotake-Cho, Miyazaki, 889-1692, Japan. Address e-mail to oni{at}shaw.ca

Lidocaine causes both inhibition and excitation in the central nervous system, including the respiratory pattern. The excitation induced by an excessive dose of local anesthetic is thought to be the result of an initial blockade of an inhibitory pathway in the cerebral cortex. To clarify the effect of lidocaine on the pre- and postsynaptic neurons of an inhibitory synapse, a cultured soma-soma respiratory pattern generator model consisting of two neurons from the snail Lymnaea stagnalis were reconstructed in vitro. First we investigated the effects of lidocaine on single presynaptic (RPeD1) or postsynaptic (VD4) neurons. While RPeD1 and VD4 were simultaneously recorded, the number of action potentials, the membrane potential, and the wavelength of the action potential were compared before and after lidocaine (0.01, 0.1, and 1 mM) administration. Lidocaine increased the number of action potentials and the wavelength of a single action potential, and it depolarized the resting membrane potential in both RPeD1 and VD4 neurons in a dose-dependent manner. Furthermore, lidocaine decreased outward potassium currents. In soma-soma pairs, RPeD1 excitation and VD4 suppression occurred in 0.01 mM lidocaine, whereas both RPeD1 and VD4 neurons were excited by 0.1 and 1 mM lidocaine. In conclusion, lidocaine causes a reduction in synaptic transmission and general neuronal excitation in both presynaptic and postsynaptic neurons.

IMPLICATIONS: Lidocaine reduces inhibitory synaptic transmission. However, lidocaine induces a decrease in the outward voltage-gated potassium current, which leads to depolarization and general excitation of both presynaptic and postsynaptic neurons. Lidocaine’s side effects, such as convulsion, seizure, and hyperventilation, may result from such changes in general neuronal excitability.







Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 2005 by the International Anesthesia Research Society.