Actions of General Anesthetics on Acetylcholine Receptor-rich Membranes from Torpedo californica

Firestone, Leonard L.; Sauter, JF; Braswell, Leon M.; Miller, Keith W.

doi:10.1097/00000542-198606000-00004

Cited by 47 publications

(16 citation statements)

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“…They are also in a good agreement with the EC 50 values for iso¯urane anaesthesia, which occurs at 290 mM for tadpoles (Firestone et al, 1986). Comparable aqueous concentrations can also be calculated based on the minimum alveolar concentration (MAC) for mice (320 mM), rats (350 mM), and humans (310 mM) (Franks & Lieb, 1993).…”

Section: Discussionsupporting

confidence: 71%

Concentration‐dependent isoflurane effects on depolarization‐evoked glutamate and GABA outflows from mouse brain slices

Liachenko

Tang

Somogyi

et al. 1999

British J Pharmacology

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1 The synaptic concentrations of glutamate and g-aminobutyric acid (GABA) are modulated by their release and re-uptake. The e ects of general anaesthetics on these two processes remain unclear. This study evaluates the e ects of iso¯urane, a clinically important anaesthetic, on glutamate and GABA release and re-uptake in superfused mouse cerebrocortical slices. 2 Experiments consisted of two 1.5-min exposures to 40 mM KCl in 30 min intervals. During the second exposure, di erent concentrations of iso¯urane with and without 0.3 mM L-transpyrrolidine-2,4-dicarboxylic acid (PDC, a competitive inhibitor of glutamate uptake transporter) or 1 mM nipecotic acid (a competitive inhibitor of GABA uptake transporter) were introduced. The ratios of the second to ®rst KCl-evoked increases in glutamate and GABA were used to determine the iso¯urane concentration-response curves.3 The results can be described as a sum of two independent processes, corresponding to the inhibitions of release and re-uptake, respectively. The EC 50 values for the inhibitions of release and re-uptake were 295+16 and 805+43 mM for glutamate, and 229+13 and 520+25 mM for GABA, respectively. Addition of PDC did not signi®cantly a ect glutamate release but shifted the re-uptake curve to the left (EC 50 =315+20 mM). Nipecotic acid completely blocked GABA uptake, rendering iso¯urane inhibition of GABA re-uptake undetectable. 4 Our data suggest that iso¯urane inhibits both the release and re-uptake of neurotransmitters and that the inhibitions occur at di erent EC 50 's. For GABA, both EC 50 's are within the clinical concentration range. The net anaesthetic e ect on extracellular concentrations of neurotransmitters, particularly GABA, depends on the competition between inhibition of release and that of re-uptake.

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Section: Discussionsupporting

confidence: 71%

Concentration‐dependent isoflurane effects on depolarization‐evoked glutamate and GABA outflows from mouse brain slices

Liachenko

Tang

Somogyi

et al. 1999

British J Pharmacology

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“…In either case, the closed state with the alcohol molecule bound may represent a desensitized state of the channel. There is evidence from binding studies that the n-alcohols, in the presence of an agonist, enhance the extent of desensitization of nAChR channels by binding with higher affinity to the desensitized state than to the open or resting state (Firestone, Sauter, Braswell & Miller, 1986).…”

Section: Discussionmentioning

confidence: 99%

Actions of n‐alcohols on nicotinic acetylcholine receptor channels in cultured rat myotubes.

Murrell

Braun

Haydon

1991

The Journal of Physiology

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SUMMARY1. The actions of the n-alcohols from pentanol to dodecanol on nicotinic acetylcholine receptor (nAChR) channels were investigated by recording single AChactivated channel activity from inside-out membrane patches isolated from cultured rat myotubes. Alcohols were applied to the cytoplasmic side of the membrane; aqueous concentrations ranged from 11 7 mM-pentanol to 0-02 mm-dodecanol.2. The intermediate-chain alcohols (pentanol to octanol) caused channel currents to fluctuate between the fully open and closed state level so that openings occurred in bursts interrupted by brief gaps. Closed time distributions were fitted well with two exponential components, the fast component representing the closures within a burst. The number of gaps within a burst was dependent on alcohol concentration whereas gap duration was independent of concentration but increased with increasing chain length of the alcohol up to octanol.3. Nonanol and decanol reduced the mean duration of bursts of openings but did not cause an increase in the number of short closed intervals within a burst. Beyond decanol there was a decline in the ability of the n-alcohols to affect channel function. A saturated solution of undecanol (0-07 mM) reduced the mean open time by 33+17 %, whereas a saturated solution of dodecanol had no significant effect. Over the range of concentrations tested this describes the effects of all the n-alcohols (C5 to C12) on channel gating reasonably well.6. Blocking rate constants (k+B) for pentanol through to nonanol were calculated to be between 2 8 and 5-7 x 106 M-1 s-1. These values are based on the assumption that the concentration of the alcohols at their site(s) of action was equal to the aqueous concentration applied to the membrane.

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“…However, it is known that halothane increases the binding of acetylcholine to the acetylcholine receptor of the Torpedo electroplax (Firestone et al, 1986) and this may also be true of its action on the nicotinic receptor of the chromaffin cell. If this is so, the higher affinity binding must reflect a desensitized state, as suggested by Firestone et al (1986). Alternatively it, and the other agents we have studied, may act directly on the ion channel associated with the nicotinic receptor.…”

Section: Discussionmentioning

confidence: 99%

The action of volatile anaesthetics on stimulus‐secretion coupling in bovine adrenal chromaffin cells

Pocock

Richards

1988

British J Pharmacology

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1 The action of four volatile anaesthetics, ethrane, halothane, isoflurane and methoxyflurane on stimulus-secretion coupling has been studied in isolated bovine adrenal medullary cells. All four agents inhibited the secretion of adrenaline and noradrenaline evoked by 5001iM carbachol at concentrations within the anaesthetic range. Total catecholamine secretion induced by stimulation with 77mM potassium was also inhibited but at higher concentrations. All four agents inhibited the 45Ca influx evoked by stimulation with 500pM carbachol and the 45Ca influx in response to K+-depolarization. 2 When total catecholaIiine secretion in response to potassium or carbachol was modulated by varying extracellular calcium or by adding halothane or methoxyflurane to the incubation medium, the amount of catecholamine secretion for a given Ca2 + entry was the same. 3 The action of methoxyflurane on the relationship between intracellular free Ca and exocytosis was examined using electropermeabilised cells, which were suspended in solutions containing a range of concentrations of ionised calcium between 10 -8 and 10-M. The anaesthetic had no effect on the activation of exocytosis by intracellular free calcium. 4 Halothane and methoxyflurane inhibited the carbachol-induced secretion of catecholamines in a non-competitive manner. 5 Halothane and methoxyflurane inhibited the increase in 22Na influx evoked by carbachol. For halothane and methoxyflurane this inhibition of Na influx appears to be sufficient to account for the inhibition of the evoked catecholamine secretion. 6 We conclude that the volatile anaesthetics ethrane, halothane, isoflurane and methoxyflurane inhibit the secretion of adrenaline and noradrenaline induced by carbachol at concentrations that lie within the range encountered during general anaesthesia. In addition all four also inhibit the secretion of catecholamines induced by depolarization with 77 mM K+ but at much higher concentrations. The decrease in Ca influx caused by methoxyflurane accounts fully for the decrease in secretion in response to depolarization with potassium. Similar actions at synapses within the CNS may underlie the general anaesthetic effects of these agents.

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Actions of General Anesthetics on Acetylcholine Receptor-rich Membranes from Torpedo californica

Cited by 47 publications

References 0 publications

Concentration‐dependent isoflurane effects on depolarization‐evoked glutamate and GABA outflows from mouse brain slices

Concentration‐dependent isoflurane effects on depolarization‐evoked glutamate and GABA outflows from mouse brain slices

Actions of n‐alcohols on nicotinic acetylcholine receptor channels in cultured rat myotubes.

The action of volatile anaesthetics on stimulus‐secretion coupling in bovine adrenal chromaffin cells

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