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Two types of TTX‐resistant and one TTX‐sensitive Na + channel in rat dorsal root ganglion neurons and their blockade by halothane
Author(s) -
Scholz A.,
Appel N.,
Vogel W.
Publication year - 1998
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.1998.00268.x
Subject(s) - halothane , tetrodotoxin , dorsal root ganglion , chemistry , biophysics , kinetics , blockade , electrophysiology , neuroscience , anesthesia , spinal cord , biochemistry , medicine , receptor , biology , physics , organic chemistry , quantum mechanics
The clinically employed general anaesthetic halothane was shown to exert action on the peripheral nervous system by suppressing spinal reflexes, but it is still unclear which mechanisms underlie this action. The present study addressed the question whether blockade of tetrodotoxin‐sensitive (TTXs) and ‐resistant (TTXr) Na + ‐channels in rat dorsal root ganglia (DRG) neurons by halothane could explain its peripheral effects. Two types of TTXr Na + ‐currents, fast and slow, with distinct activation and inactivation kinetics were found in small (< 25 μm) and medium sized (25–40 μm) DRG neurons. These currents were blocked by halothane with IC 50 values of 5.4 and 7.4 mmol/L, respectively. Additionally, in a concentration‐dependent manner halothane accelerated the inactivation kinetics of both currents and shifted the inactivation curves 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 contrast to that of fast current, the time‐to‐peak for slow current was changed in the presence of halothane. The TTXs Na + ‐current which prevailed in large neurons (> 40 μm) was blocked by halothane with an IC 50 of 12.1 mmol/L. Its inactivation curve was also shifted to more hyperpolarized potentials and the inactivation kinetics accelerated with increasing halothane concentration. Similarly to TTXr Na + ‐currents, the activation curve of TTXs Na + ‐current and its time‐to‐peak were not influenced 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 the incomplete reduction of spinal reflexes at clinically used concentrations of halothane.