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

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 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.

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.

• Authors: Mu Yu, Lin Chen
• Journal: Acta pharmacologica Sinica (Acta Pharmacol Sin) Vol. 29 Issue 12 Pg. 1409-18 (Dec 2008) ISSN: 1745-7254 [Electronic] United States
• PMID: 19026159 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anesthetics, Local
• Ion Channels
• gamma-Aminobutyric Acid
• Lidocaine

Topics

• Action Potentials (drug effects, physiology)
• Anesthetics, Local (pharmacology)
• Animals
• Cells, Cultured
• Dose-Response Relationship, Drug
• Humans
• Inferior Colliculi (cytology, drug effects, metabolism)
• Ion Channel Gating (drug effects)
• Ion Channels (metabolism)
• Lidocaine (pharmacology)
• Neurons (drug effects, metabolism)
• Patch-Clamp Techniques
• Rats
• Rats, Wistar
• gamma-Aminobutyric Acid (metabolism)