Selective Action of Anesthetics on Synapses and Axons in Mammalian Sympathetic Ganglia

1 It has been suggested that the depression of excitatory synaptic potentials produced by general anaesthetics can be attributed to°la partial blockade of impulse conduction in the terminal branches of axons. This hypothesis has been tested by comparing the actions of pentobarbitone, procaine and tetrodotoxin (TTX) on synaptic transmission in the guinea-pig olfactory cortex. 2 Pentobarbitone (0.1-0.3 mM) depressed the evoked synaptic potentials without any significant depression of impulse conduction in the afferent fibres of the lateral olfactory tract (l.o.t.). It had no effect on the electrical excitability of either the l.o.

Section: Resultssupporting

confidence: 94%

The Actions of Pentobarbitone, Procaine and Tetrodotoxin on Synaptic Transmission in the Olfactory Cortex of the Guinea‐pig

Richards

1982

“…If, however, the dose was doubled or trelbled a marked conduction block developed. This is wholly in agreement with the findings of Larrabee & Posternak (1952), who used the more simple synaptic system of the superior cervical ganglion of the cat. S6mjen (1963) also demonstrated no impairment of conduction in afferent fibres in the cat spinal cord with concentrations of ether which were sufficient to blook reflex discharge, but he pointed out that this does not eliminate the possiibility of a conduction block in fine terminals, for a microelectrode may be recording activity mainly from the parent axons.…”

Section: Discussionsupporting

confidence: 91%

Microelectrode studies in the frog isolated spinal cord during depression by general anaesthetic agents

Richens

1969

. Extracellular and intracellular potentials have been recorded from the isolated spinal cord of the frog during depression of synaptic transmission by volatile and barbiturate general anaesthetic agents. . Volatile agents did not impair conduction in presynaptic terminals in concentrations which completely blocked synaptic transmission. . Methohexitone consistently impaired conduction in presynaptic terminals long before transmission through polysynaptic pathways was blocked. . Volatile agents depressed the excitability of the motoneurone membrane, as evidenced by impaired antidromic invasion, reduced excitability to direct stimulation, depression of the synaptic potential and elevation of firing threshold. It is concluded that these actions are responsible for the depressant effect of volatile agents on spinal reflexes. . Methohexitone produced an increase in the excitability of the motoneurone membrane, as evidenced by enhanced antidromic invasion, increased excitability to direct stimulation and potentiation of short latency responses. Despite this excitatory action, the polysynaptic pathways through the cord were depressed by an action of the drug on conduction in presynaptic terminals. . It is suggested that the sensitivity of the motoneurone membrane to volatile agents may contribute to the good muscle relaxant properties of these drugs in clinical use.

“…Since Sherrington (1906) drew attention to the susceptibility of reflex arcs, attention has focussed on the synapse as the site of action of anaesthetic drugs. It has become apparent that anaesthetics differ in their actions at individual synapses (Larrabee & Posternak, 1952) and that different central nervous pathways have unequal sensitivities (Mark & Steiner, 1958). Indeed some such differential action is required to explain the characteristic clinical states which follow administration of the various drugs (Vickers, Wood-Smith & Stweart, 1978).…”

Section: Introductionmentioning

confidence: 99%

Dissimilar Influences of Some Injectable Anaesthetics on the Responses of Reticulospinal Neurones to Inhibitory Transmitters in the Lamprey

Cullen¹,

Martin²

1982

Intracellular recordings were made from identified bulbar reticulo‐spinal neurones in the medulla of lamprey ammocoetes. Responses to iontophoretically applied inhibitory transmitters were measured as changes in membrane potential and input resistance. Dose‐dependent alterations in the responses to γ‐aminobutyric acid (GABA) and glycine during bath application of injectable anaesthetic drugs were measured; the compounds used were pentobarbitone, ketamine, metomidate and the steroid mixture alphaxalone/alphadolone (Saffan). GABA responses were potentiated by pentobarbitone (1–3 × 10−4m) and prolonged by ketamine (3.7 × 10−5m); but depressed by high concentrations (10−3m) of all drugs, as well as by anaesthetic concentrations of alphaxalone (1–3 × 10−5m). Glycine responses were depressed by alphaxalone (1–3 × 10−5m) and by supra‐anaesthetic concentrations of ketamine (3.7 × 10−4 m) and metomidate (1.8 × 10−3m). No drug potentiated the glycine responses. In the absence of an effect common to the 4 anaesthetics, it is concluded that neither potentiation nor inhibition of all GABA or glycine responses is an essential feature of anaesthesia. However, effects comparable to those described here may contribute to the overall clinical picture during anaesthesia of higher vertebrates. The findings do not support the notion that all anaesthetic agents act on biological membranes by a single mechanism.