2 TYPES OF TTX-RESISTANT AND ONE TTX-SENSITIVE NA-ROOT GANGLION NEURONS AND THEIR BLOCKADE BY HALOTHANE( CHANNEL IN RAT DORSAL)

The clinically employed general anaesthetic halothane was shown to exe rt action on the peripheral nervous system by suppressing spinal refle xes, but it is still unclear which mechanisms underlie this action. Th e present study addressed the question whether blockade of tetrodotoxi n-sensitive (TTXs) and -resistant (TTXr) Na+- channels in rat dorsal r oot ganglia (DRG) neurons by halothane could explain its peripheral ef fects. Two types of TTXr Na+-currents, fast and slow, with distinct ac tivation and inactivation kinetics were found in small (< 25 mu m) and medium sized (25-40 mu m) DRG neurons. These currents were blocked by halothane with IC50 values of 5.4 and 7.4 mmol/L, respectively. Addit ionally, in a concentration-dependent manner halothane accelerated the inactivation kinetics of both currents and shifted the inactivation c urves to more hyperpolarized potentials. Neither the activation curves of both TTXr Na+-currents were influenced by halothane nor a voltage- dependent block at test potentials of the currents was seen. In contra st to that of fast current, the time-to-peak for slow current was chan ged in the presence of halothane. The TTXs Na+-current which prevailed in large neurons (> 40 mu m) was blocked by halothane with an IC50 of 12.1 mmol/L. Its inactivation curve was also shifted to more hyperpol arized potentials and the inactivation kinetics accelerated with incre asing halothane concentration. Similarly to TTXr Na+-currents, the act ivation curve of TTXs Na+-current and its time-to-peak were not influe nced by halothane. It is suggested that two types of TTXr Na+-currents can explain the heterogeneity in kinetic data for TTXr Na+-currents. Furthermore, the incomplete blockade of Na+-currents might underlie th e incomplete reduction of spinal reflexes at clinically used concentra tions of halothane.