Vol. 299, Issue 2, 705-711, November 2001

Lithium Increases Potency of Lidocaine-Induced Block of Voltage-Gated Na⁺ Currents in Rat Sensory Neurons in Vitro

Michael S. Gold and Paul D. Thut

Departments of Oral and Craniofacial Biological Sciences and Anatomy and Neurobiology, and the Program in Neuroscience, University of Maryland, Baltimore, Maryland

We and others have obtained data both in vivo and in isolated nerve preparations suggesting that Li⁺ increases the potency of local anesthetics in the block of conduction. In the present study we have tested the hypothesis that Li⁺ increases the potency of local anesthetic-induced block of conduction via a shift in the potency of local anesthetic-induced block of voltage-gated Na⁺ channels. To test this hypothesis we have used whole cell patch-clamp electrophysiological techniques on isolated adult rat sensory neurons. The presence of Li⁺ significantly increased the potency of lidocaine-induced block of both tetrodotoxin (TTX)-sensitive and TTX-resistant voltage-gated Na⁺ currents: ED₅₀ values for lidocaine-induced block of both currents in the presence of Li⁺ were less than 35% of the values obtained in the presence of Na⁺. Li⁺ effects were dependent on the state of the Na⁺ channel. It increased the potency of lidocaine-induced block of resting or closed channels, without a detectable influence on use-dependent block or block of channels in the inactivated state. Li⁺ alone had no detectable effect on the gating properties of voltage-gated Na⁺ currents present in sensory neurons. The effects of Li⁺ were concentration-dependent. These results support the suggestion that the influence of Li⁺ on lidocaine-induced conduction block reflects an increase in potency of lidocaine-induced block of voltage-gated Na⁺ channels. This increase in potency appears to reflect an increase in the affinity of the low-affinity binding site for local anesthetics. Including Li⁺ in lidocaine preparations may be an effective way to increase the safety factor associated with the use of this anesthetic clinically.