Lithium increases potency of lidocaine-induced block of voltage-gated Na+ currents in rat sensory neurons in vitro.
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.
Gold
M S
MS
Department of Oral and Craniofacial Biological Sciences, University of Maryland, Baltimore Dental School, Baltimore, MD 21201 USA. msg001@dental.umaryland.edu
Thut
P D
PD
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D004357:Drug Synergism; D004558:Electric Stimulation; D004594:Electrophysiology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D008012:Lidocaine / Q000494:pharmacology*; D008094:Lithium / Q000494:pharmacology*; D009475:Neurons, Afferent / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin; D008012:Lidocaine; D008094:Lithium