Selective block of late Na(+) current by local anaesthetics in rat large sensory neurones.
The actions of lignocaine and benzocaine on transient and late Na(+) current generated by large diameter (> or =50 microm) adult rat dorsal root ganglion neurones, were studied using patch-clamp techniques. Both drugs blocked whole-cell late Na(+) current in a concentration-dependent manner. At 200 ms following the onset of a clamp step from -110 to -40 mV, the apparent K for block of late Na(+) current by lignocaine was 57.8+/-15 microM (mean+/-s.e.mean, n = 4). The value for benzocaine was 24.9+/-3.3 microM, (mean+/-s.e. mean, n = 3). The effect of lignocaine on transient current, in randomly selected neurones, appeared variable (n = 8, half-block from approximately 50 to 400 microM). Half-block by benzocaine was not attained, but both whole-cell (n = 11) and patch data suggested a high apparent K,>250 microM. Transient current always remained after late current was blocked. The voltage-dependence of residual late current steady-state inactivation was not shifted by 20 microM benzocaine (n = 3), whereas 200 microM benzocaine shifted the voltage-dependence of transient current steady-state inactivation by -18.7+/-5.9 mV (mean+/-s.e.mean, n = 4). In current-clamp, benzocaine (250 microM) could block subthreshold, voltage-dependent inward current, increasing the threshold for eliciting action potentials, without preventing their generation (n = 2). Block of late Na(+) current by systemic local anaesthetic may play a part in preventing ectopic impulse generation in sensory neurones.
Baker
M D
MD
Sobell department of Neurophysiology, Institute of Neurology, Queen Square, London WC1N 3BG.
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D001566:Benzocaine / Q000494:pharmacology*; D002478:Cells, Cultured; D004594:Electrophysiology; D008012:Lidocaine / Q000494:pharmacology*; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D026941:Sodium Channel Blockers
D000779:Anesthetics, Local; D026941:Sodium Channel Blockers; D008012:Lidocaine; D001566:Benzocaine