Effect of halothane on neuronal excitation in the superficial dorsal horn of rat spinal cord slices: evidence for a presynaptic action.
The action of the volatile anaesthetic halothane on optically recorded neuronal excitation in juvenile rat spinal cord slices was investigated. Prolonged neuronal excitation lasting approximately 100 ms was evoked in the superficial dorsal horn after single-pulse dorsal root stimulation that activated both A- and C-fibres. Halothane depressed the neuronal excitation in a concentration-dependent manner (IC(50) 0.21 mm, I(max) 28%). In Ca(2+)-free solution, dorsal root stimulation induced excitation with a short duration of several tens of milliseconds, in which the excitation of the postsynaptic component was largely eliminated. Under these conditions, halothane also depressed the excitation concentration-dependently (IC(50) 0.46 mm, I(max) 60%). Most of the suppression occurred within 5 min of halothane application, and the effect of halothane was fully reversible upon washout of the anaesthetic. Application of bicuculline and strychnine or picrotoxin, or reduction of extracellular Cl(-) concentration ([Cl(-)](o)), had no effect on halothane inhibition. Applications of K(+) channel blockers tetraethyl ammonium, 4-aminopyridine, Cs(+) or Ba(2+) either had no effect or augmented the inhibitory effect of halothane. On the other hand, the degree of inhibition by halothane was found to be dependent on [K(+)](o); the higher [K(+)](o), the larger the depression. In addition, decreases in [Na+]o and [Mg(2+)](o) reduced the excitation similar to that of halothane treatment, and the degree of halothane inhibition became larger with lower [Mg(2+)](o). These results lead to a hypothesis that halothane suppresses the excitation of presynaptic elements by inhibiting presynaptic Na(+) channels by shifting the steady-state inactivation curve in the hyperpolarizing direction.
Asai
Tatsuya
T
Department of Human and Artificial Intelligence Systems, Fukui University, 3-9-1 Bunkyo, Fukui 910-8507, Japan. asai@synapse.fuis.fukui-u.ac.jp
Kusudo
Kei
K
Ikeda
Hiroshi
H
Takenoshita
Makoto
M
Murase
Kazuyuki
K
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000344:Afferent Pathways / Q000187:drug effects* / Q000502:physiology; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000172:deficiency; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D018118:Chloride Channels / Q000187:drug effects / Q000378:metabolism; D004558:Electric Stimulation; D001330:Electronic Data Processing; D006221:Halothane / Q000494:pharmacology*; D008274:Magnesium / Q000494:pharmacology; D009412:Nerve Fibers / Q000187:drug effects* / Q000502:physiology; D009619:Nociceptors / Q000187:drug effects* / Q000502:physiology; D009924:Organ Culture Techniques; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000502:physiology; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000187:drug effects / Q000378:metabolism; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D018009:Receptors, Glycine / Q000187:drug effects / Q000378:metabolism; D012964:Sodium / Q000494:pharmacology
D018685:Anesthetics, Inhalation; D018118:Chloride Channels; D015221:Potassium Channels; D018079:Receptors, GABA; D017470:Receptors, Glutamate; D018009:Receptors, Glycine; D012964:Sodium; D008274:Magnesium; D011188:Potassium; D002118:Calcium; D006221:Halothane