THE ACTION OF GENERAL ANAESTHETICS ON ACETYLCHOLINE‐INDUCED INHIBITION IN THE CENTRAL NERVOUS SYSTEM OF Helix

1 Completely isolated identified neurones from the right parietal ganglion of the pond snail Lymnaea stagnalis were studied under two-electrode voltage-clamp. Neuronal nicotinic acetylcholine receptor currents were studied at low acetylcholine (ACh) concentrations (< 200 nM). At these levels, control currents were non-desensitizing and proportional to the square of the ACh concentration. 2 IC50 concentrations were determined for the steady-state inhibition of the ACh-activated current by 31 general anaesthetics plus the non-anaesthetic alcohol n-tridecanol. The general anaesthetics included inhalational agents, n-alcohols, n-alkane-(a,)-diols, cycloalcohols and an n-alkane. 3 Anaesthetic inhibition was independent of voltage and consistent with two anaesthetic-binding sites on the receptor. 4 IC50 concentrations for inhibiting the neuronal nicotinic ACh receptor correlated well (r = 0.97) with EC50 concentrations for general anaesthesia. The maximum deviation from the line of identity was less than fourfold. The inhalational agents tended to be more potent as inhibitors of the ACh receptor than as general anaesthetics, while the alcohols and diols were less potent. 5 The inhibition of the ACh-induced current by the homologous series of n-alcohols exhibited a cutoff at the same position (just after dodecanol) as found for the induction of general anaesthesia in tadpoles. 6 Polarity profile maps of the anaesthetic-binding sites on the neuronal nicotinic ACh receptor were calculated from IC50 concentrations for the homologous series of n-alcohols and n-alkane-(a,)-diols.They reveal amphiphilic sites with apolar regions capable of accommodating the hydrocarbon chains of n-alcohols as large as decanol. A striking resemblance was found to profiles previously calculated from data for tadpole general anaesthesia.

Section: Resultssupporting

confidence: 92%

Actions of general anaesthetics on a neuronal nicotinic acetylcholine receptor in isolated identified neurones of Lymnaea stagnalis

McKenzie

Franks

Lieb

1995

“…A depressant or blocking action of pentobarbitone has been well described at acetylcholine (ACh)-gated chloride channels in invertebrates (Adams et al, 1982;Judge & Norman, 1982;Wachtel & Wilson, 1983 (Robertson, 1989). Judge & Norman (1982) Nicoll & Wojtowicz (1980) and Nicoll & Madison (1982). This anaesthetic also produced steady state currents and relaxations opposite in direction to those seen with GABA, which are consistent with some form of blocking behaviour.…”

Section: Halothane Ketamine and Diazepamsupporting

confidence: 52%

“…Peters et al (1988) have also observed a marked bounce on washout of high concentrations of pentobarbitone, and suggest these high concentrations had blocking activity on GABAA chloride channels. A depressant or blocking action of pentobarbitone has been well described at acetylcholine (ACh)-gated chloride channels in invertebrates (Adams et al, 1982;Judge & Norman, 1982;Wachtel & Wilson, 1983 (Robertson, 1989). Judge & Norman (1982) Nicoll & Wojtowicz (1980) and Nicoll & Madison (1982).…”

Section: Halothane Ketamine and Diazepammentioning

confidence: 99%

Actions of anaesthetics and avermectin on GABA_A chloride channels in mammalian dorsal root ganglion neurones

Robertson

1989

1 The y-aminobutyric acid (GABA)-mimetic actions of some anaesthetics and the antehelminthic avermectin B1a were examined on freshly isolated mammalian dorsal root ganglion (DRG) neurones by use of suction electrodes and a single electrode voltage clamp.2 Pentobarbitone (60yM-3mM), chloralose (600yM-1mM), etomidate (10-100 pM), alphaxalone (10-60pM) and avermectin (10-60pM) directly activated chloride channels in GABA-sensitive DRG neurones. The agonist action was sensitive to block by bicuculline and picrotoxinin. 3 Steady-state current-voltage (I-V) curves for the anaesthetics were either linear, or rectified in the opposite direction to steady-state I-V curves obtained with GABA. Current relaxations in response to voltage jumps were also of the opposite direction. An extra surge of current ('bounce') was commonly observed on washout of some of these agonists. 4 Pentobarbitone was ineffective as an agonist at alkali pH (10.4 and 9.4), but was approximately twice as effective at acid (5.4) than at normal (7.4) pH values. 5 These results suggest that some anaesthetics and avermectin are capable of 'blocking' GABA channels in addition to activating them.

“…Judge & Norman (1982) showed that general anaesthetics depressed the Cl-dependent inhibitory response to ACh in Helix neurones. In the present study, enflurane depressed both excitatory and inhibitory ACh-responses in a dose-dependent manner and the K-dependent response was less sensitive to the anaesthetic.…”

Section: Discussionmentioning

confidence: 99%

“…Block of excitatory transmission occurs at much lower anaesthetic concentrations than blockage of axonal conduction of action potentials (Larrabee & Posternak, 1952;Richards & White, 1975). In molluscan preparations, both excitatory (Barker, 1975) and inhibitory (Cote & Wilson, 1980;Judge & Norman, 1982) synaptic responses may be depressed by anaesthetics. Volatile 'Author for correspondence. anaesthetics including enflurane have depressant effects at the neuromuscular junction (Gage & Hamill, 1976).…”

Section: Introductionmentioning

confidence: 99%

Action of enflurane on cholinergic transmission in identified Aplysia neurones

Arimura

Ikemoto

1986

Effects of enflurane on the cholinergic transmission in Aplysia neurones were studied by current and voltage clamp methods. Acetylcholine (ACh) evoked three types of postsynaptic responses on different identified neurones: (1) a depolarizing response due to an increase in Na and K conductances (D‐response), (2) a fast hyperpolarizing response due to an increase in Cl conductance (Cl‐response), and (3) a slow hyperpolarizing response due to an increase in K conductance (K‐response). Enflurane altered neither the action potential nor the membrane resistance of the neurones but depressed the three ACh‐induced responses, non‐competitively, in a dose‐dependent manner. The K‐response was less suppressed than the other two. Blockade of the closed state of ion channel was suggested by a reduction in the first ACh response evoked 1 min after administration of enflurane. The anaesthetic facilitated the decay of the neurally evoked e.p.s.c. and i.p.s.c. in suggesting a reduction in the mean open time of the postsynaptic ion channel. It is concluded that enflurane depresses excitatory and inhibitory cholinergic transmission by reducing the postsynaptic currents.