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Keywords:

  • lidocaine;
  • tinnitus;
  • inferior colliculus;
  • sodium channel;
  • potassium channel;
  • glycine receptor;
  • GABAA receptor;
  • N-methyl-D-aspartate receptor;
  • whole-cell patch-clamp

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.