Halothane depresses action potential conduction in hippocampal axons.
General anesthetics are thought to depress the central nervous system (CNS) by acting at synapses; however, only a few studies have compared effects on axonal conduction with effects on synaptic responses using mammalian CNS preparations. The present study used glutamate receptor antagonists (CNQX/APV) or low calcium to block synaptic transmission, allowing Schaffer-collateral axon fiber volleys to be recorded from rat hippocampal brain slices. Since fiber volleys are compound action potentials, they provide a measure of axonal conduction in Schaffer-collateral fibers. Clinical concentrations of the inhalational anesthetic, halothane (1 rat MAC, 1.2 vol.%), produced an 18 +/- 2.3% depression of fiber volley amplitudes (mean +/- S.D.; p < 0.001 ANOVA, n = 10). Depression of action potential conduction accounted for approximately 30% of the overall depression of synaptic transmission produced by halothane at this concentration. Halothane-induced fiber volley depression occurred with little change in conduction velocity, similar to the effect seen with decreased stimulus intensity, but significantly different from the decreased velocity produced by tetrodotoxin (100 nM, p < 0.005). The results indicate that halothane can depress axonal conduction at clinically relevant concentrations and that this depression could contribute to the CNS depression that is associated with anesthesia.
Stanford Neuroscience Program, Department of Anesthesia, Stanford University School of Medicine, CA 94305-5117, USA.
A A
AA
Mikulec
S
S
Pittson
S M
SM
Amagasu
F A
FA
Monroe
M B
MB
MacIver
D000200:Action Potentials / Q000187:drug effects; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006221:Halothane / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D009431:Neural Conduction / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects
D018685:Anesthetics, Inhalation; D006221:Halothane