Local anaesthetic effects on tetrodotoxin-resistant Na+ currents in rat dorsal root ganglion neurones.

Abstract

Besides the fast tetrodotoxin-sensitive Na+ current, small dorsal root ganglion neurones of rats also possess a slower tetrodotoxin-resistant Na+ current. The blocking effect of commonly used local anaesthetics upon the tetrodotoxin-resistant Na+ current was investigated in the present paper. Dorsal root ganglia were dissected from adult rats and cells were enzymatically isolated. The whole-cell patch clamp technique was then used to measure inward Na+ currents of small dorsal root ganglion neurones. Externally applied local anaesthetics reversibly blocked the tetrodotoxin-resistant Na+ current in a dose-dependent manner. Half-maximal blocking concentrations for tonic block were: lignocaine, 326 microM; prilocaine, 253 microM; mepivacaine, 166 microM; etidocaine, 196 microM bupivacaine, 57 microM procaine, 518 microM benzocaine, 489 microM; tetracaine, 21 microM; and dibucaine, 23 microM. Blocking of the current by lignocaine was independent of temperature. The quaternary lignocaine derivative OX-314 did not have any effect upon the tetrodotoxin-resistant Na+ current when applied externally. High concentrations of tetrodotoxin also blocked the tetrodotoxin-resistant Na+ current with a half-maximal blocking concentration of 115 microM. The block by high tetrodotoxin concentrations did not compete with the lignocaine block, suggesting that there were two independent blocking mechanisms for the two substances. The tetrodotoxin-resistant Na+ currents also showed a marked sensitivity to phasic (use-dependent) block by local anaesthetics.