Modulation of major voltage- and ligand-gated ion channels in cultured neurons of the rat inferior colliculus by lidocaine1

Authors

  • Mu YU,

    1. Auditory Research Laboratory, School of Life Sciences, University of Science and Technology of China, Hefei 230027, China
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  • Lin CHEN

    Corresponding author
    1. Auditory Research Laboratory, School of Life Sciences, University of Science and Technology of China, Hefei 230027, China
    2. Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei 230027, China
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  • 1

    Project supported by grants from the National Natural Science Foundation of China (No 30470560 and 30730041), the National Basic Research Program of China (No 2007CB512306), and the CAS Knowledge Innovation Project (No KSCX1-YW-R-36).

Correspondence to Dr Lin CHEN. Phn 86-551-360-6458. E-mail linchen@ustc.edu.cn

Abstract

Aim: The purpose of the present study was to explore how lidocaine as a therapeutic drug for tinnitus targets voltage-and ligand-gated ion channels and changes the excitability of central auditory neurons. Methods: Membrane currents mediated by major voltage-and ligand-gated channels were recorded from primary cultured neurons of the inferior colliculus (IC) in rats with whole-cell patch-clamp techniques in the presence and absence of lidocaine. The effects of lidocaine on the current-evoked firing of action potentials were also examined. Results: Lidocaine at 100 μmol/L significantly suppressed voltage-gated sodium currents, transient outward potassium currents, and the glycine-induced chloride currents to 87.66 ± 2.12%, 96.33 ± 0.35%, and 91.46 ± 2.69% of that of the control level, respectively. At 1 mmol/L, lidocaine further suppressed the 3 currents to 70.26 ± 4.69%, 62.80 ± 2.61%, and 89.11 ± 3.17% of that of the control level, respectively. However, lidocaine at concentrations lower than 1 mmol/L did not significantly affect GABA-or aspartate-induced currents. At a higher concentration (3 mmol/L), lidocaine slightly depressed the GABA-induced current to 87.70 ± 1.87% of that of the control level. Finally, lidocaine at 100 μmol/L was shown to significantly suppress the current-evoked firing of IC neurons to 58.62 ± 11.22% of that of the control level, indicating that lidocaine decreases neuronal excitability. Conclusion: Although the action of lidocaine on the ion channels and receptors is complex and non-specific, it has an overall inhibitory effect on IC neurons at a clinically-relevant concentration, suggesting a central mechanism for lidocaine to suppress tinnitus.

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