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 (50 μm) 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 μ M (mean±s.e.mean, n =4). The value for benzocaine was 24.9±3.3 μ M , (mean±s.e.mean, n =3). The effect of lignocaine on transient current, in randomly selected neurones, appeared variable ( n =8, half‐block from ∼50 to 400 μ M ). Half‐block by benzocaine was not attained, but both whole‐cell ( n =11) and patch data suggested a high apparent K ,>250 μ M . Transient current always remained after late current was blocked. The voltage‐dependence of residual late current steady‐state inactivation was not shifted by 20 μ M benzocaine ( n =3), whereas 200 μ M 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 μ M ) 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.British Journal of Pharmacology (2000) 129 , 1617–1626; doi: 10.1038/sj.bjp.0703261