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

Abstract

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.

Effects of injectable anaesthetics on responses to L‐glutamate and on spontaneous synaptic activity in lamprey reticulo‐spinal neurones

“…The pharmacology of the glutamate receptor present on lamprey reticulo-spinal cells has not been studied in detail but any NMDA receptors present should be inhibited by the 15 mM Mg2" used (Evans & Watkins, 1978;Ault et al, 1980 (Richards & Smaje, 1976). Alphaxalone's and metomidate's failure to depress glutamate responses markedly at low concentrations should reinforce the block of responses to inhibitory amino acids that we have described previously (Cullen & Martin, 1982). It was a general finding that the i.p.s.ps were more susceptible to anaesthetic blockade.…”

“…The most striking feature of these experiments was the lesser effect of anaesthetics on glutamate than on GABA and glycine responses (compare Cullen & Martin, 1982), despite the fact that small changes in membrane conductance would exert a more readily detectable effect on the glutamate response, whose reversal potential (about -35 mV: Matthews & Wickelgren, 1979) is far from the resting potential. This contrast, which was particularly dramatic with metomidate, indicates that the depressant effects of high concentrations of all the anaesthetics on the inhibitory responses cannot be the result of an entirely non-specific neuronal depression.…”

“…Krnjevic & Phillis, 1963;Crawford & Curtis, 1966;Johnson et al, 1969;Richards & Smaje, 1976;Nicoll & Wojtowicz, 1980 (Cullen & Martin, 1982). Pentobarbitone had no effect likely to increase activity in the reticulospinal axons: all effects described would be expected to reduce motor responses to stimulation and so promote muscle relaxation.…”

“…The experiments were carried out using 12-15 mm ammocoetes of the species Lampetra fluviatilis and Lampetra planeri, and methods substantially the same as those described in detail previously (Cullen & Martin, 1982). These are briefly restated here.…”

“…In many cells the glutamate-evoked change in input resistance could not be measured accurately, so measurements were confined to the peak changes in membrane potential and in the area enclosed by the envelope of the response (see Figure 2 in Cullen & Martin, 1982). The results of different experiments were combined after the proportional change in glutamate response amplitude at the peak of the drug effect had been calculated.…”