The effects of anaesthetics and high pressure on the responses of the rat superior cervical ganglion in vitro.

Abstract

SUMMARY1. The effects of helium pressure and of general anaesthetics were studied on the responses of the isolated superior cervical ganglion of the rat, to determine how far these reflected the pressure reversal of anaesthesia seen in vivo. The method of Brown & Marsh (1974) for extracellular recording of surface potentials was adapted for use in a high-pressure chamber.2. Helium alone, at 130 atm, did not alter the responses of the ganglion to y-aminobutyric acid (GABA) but significantly depressed the depolarizing and hyperpolarizing components of the nicotinic responses, and the muscarinic responses.3. The potentiation of the responses to GABA caused by pentobarbitone was not altered by the application of helium, at 130 atm. This pressure also decreased further the nicotinic responses which were depressed by pentobarbitone.4. Nitrogen, at 34 atm (the anaesthetic ED50 in vivo) and at 68 atm, significantly decreased the nicotinic responses of the ganglia, and the addition of helium to a total of 130 atm further increased this depression. At pressures of 3-3-68 atm, nitrogen caused small decreases in the responses to GABA.5. Nitrous oxide at 1-5 atm (the ED50 for loss of righting reflex in mice) and at 3 atm, significantly depressed the responses to GABA and to the nicotinic agonist, but did not alter the responses to methylfurmethide. The effects of nitrous oxide were unaltered when helium was added to a total of 130 atm, although this pressure of helium added alone significantly depressed the cholinergic responses. A mixture of 50 % nitrous oxide and 50% oxygen, when added to the pressure chamber, at normal atmospheric pressure, caused transient increases in the responses to GABA.6. The effects of temperature on GABA responses and on nicotinic responses were very different from those of pressure. Preliminary evidence suggested that raising the temperature may decrease the extent of potentiation of GABA responses by pentobarbitone.7. The results are discussed in relation to the pressure reversal of anaesthesia in vivo. It was concluded that there was no evidence that the basis of this interaction lay in the potentiation of GABA responses by general anaesthetics, or the depression of cholinergic responses, although the changes seen were not in all cases simply additive. It was considered that effects ofgeneral anaesthetics such as the potentiation of GABA may contribute to the effects used to measure general anaesthesia in vivo, 13-2 H. J. LITTLE AND D. L. THOMAS such as loss of righting reflex, but may not be related to the non-specific actions which cause anaesthesia.

Effect of Nitrous Oxide on Excitatory and Inhibitory Synaptic Transmission in Hippocampal Cultures

“…Although a lack of effect of N 2 O on GABA A receptors has been reported previously (Little and Thomas, 1986), a recent paper using isolated hippocampal neurons and a local perfusion system similar to that used here found potentiation of responses to exogenously applied muscimol (Dzoljic and Duiijn, 1998). Similarly, a study of invertebrate glutamate receptors reported blockade by N 2 O (Macdonald and Ramsey, 1995).…”

New insights into the molecular mechanisms of general anaesthetics

“…Little of the protein receptor work has approached this peculiar property of GAs. Is it an effect at the level of the whole CNS ( Halsey, 1982 ; Little and Thomas, 1986) , or is it an effect at the molecular level ( Trudell et al ., 1973a , b ; 1975 ; Chau et al ., 2007 ; 2009 )? Recent research has swung towards a protein receptor for GAs, and the evidence is quite persuasive.…”

“…Pressure reversal was observed in the action potential in peripheral nerves: high-pressure helium, itself shown not to affect nerve conduction, reversed the reduced action potential height caused by anaesthetics ( Roth et al ., 1976) . The site of action was not the sympathetic nerves in the superior cervical ganglion ( Kendig et al ., 1975) ; nor the neuromuscular junction ( Kendig and Cohen, 1976) ; nor the effect caused by a combination of pentobarbitone, N 2 O or high-pressure N 2 gas and GABA on its receptors ( Little and Thomas, 1986) .…”

“…It was not limited to GAs ( Halsey and Wardley-Smith, 1975) ; some other compounds exhibited this effect, and some GAs did not exhibit pressure reversal ( Smith et al ., 1984) . Lastly, Little and Thomas (1986) noted that helium gas alone causes hyperexcitability in the absence of anaesthetics ( Halsey, 1982) . This gas was sometimes used to increase the pressure in pressure reversal experiments.…”

“…This gas was sometimes used to increase the pressure in pressure reversal experiments. Pressure reversal may therefore be a whole-animal antagonism involving actions at separate sites, rather than a pharmacological antagonism at the GA site of action ( Little and Thomas, 1986) . Nevertheless, this is a consistently observed property of most GAs, so any hypothesis attempting to explain GA action must also provide a plausible explanation for these observations.…”