title: Modulation of major voltage- and ligand-gated ion channels in cultured neurons of the rat inferior colliculus by lidocaine.
abstract: OBJECTIVE
  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 micromol/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 mumol/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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Auditory Research Laboratory, School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
authors.forename: Mu
authors.initials: M
authors.lastname: Yu
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007245:Inferior Colliculi / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects; D007473:Ion Channels / Q000378:metabolism*; D008012:Lidocaine / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000779:Anesthetics, Local; D007473:Ion Channels; D005680:gamma-Aminobutyric Acid; D008012:Lidocaine