Biomaterial Database

Actions of general anaesthetics on a neuronal nicotinic acetylcholine receptor in isolated identified neurones of Lymnaea stagnalis. 1995

D McKenzie, and N P Franks, and W R Lieb

Biophysics Section, Blackett Laboratory, Imperial College of Science, Technology and Medicine, South Kensington, London.

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 (< or = 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-(alpha,omega)-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-(alpha,omega)-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.

UI	MeSH Term	Description	Entries
D008195	Lymnaea	A genus of dextrally coiled freshwater snails that includes some species of importance as intermediate hosts of parasitic flukes.	Lymnea,Lymnaeas,Lymneas
D008564	Membrane Potentials	The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).	Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D009474	Neurons	The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.	Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D011978	Receptors, Nicotinic	One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for NICOTINE over MUSCARINE. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, and subunit composition of the receptors.	Nicotinic Acetylcholine Receptors,Nicotinic Receptors,Nicotinic Acetylcholine Receptor,Nicotinic Receptor,Acetylcholine Receptor, Nicotinic,Acetylcholine Receptors, Nicotinic,Receptor, Nicotinic,Receptor, Nicotinic Acetylcholine,Receptors, Nicotinic Acetylcholine
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004594	Electrophysiology	The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.
D005233	Fatty Alcohols	Usually high-molecular-weight, straight-chain primary alcohols, but can also range from as few as 4 carbons, derived from natural fats and oils, including lauryl, stearyl, oleyl, and linoleyl alcohols. They are used in pharmaceuticals, cosmetics, detergents, plastics, and lube oils and in textile manufacture. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)	Fatty Alcohol,Alcohol, Fatty,Alcohols, Fatty
D000109	Acetylcholine	A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.	2-(Acetyloxy)-N,N,N-trimethylethanaminium,Acetilcolina Cusi,Acetylcholine Bromide,Acetylcholine Chloride,Acetylcholine Fluoride,Acetylcholine Hydroxide,Acetylcholine Iodide,Acetylcholine L-Tartrate,Acetylcholine Perchlorate,Acetylcholine Picrate,Acetylcholine Picrate (1:1),Acetylcholine Sulfate (1:1),Bromoacetylcholine,Chloroacetylcholine,Miochol,Acetylcholine L Tartrate,Bromide, Acetylcholine,Cusi, Acetilcolina,Fluoride, Acetylcholine,Hydroxide, Acetylcholine,Iodide, Acetylcholine,L-Tartrate, Acetylcholine,Perchlorate, Acetylcholine
D000777	Anesthetics	Agents capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general ANESTHESIA, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site.	Anesthetic,Anesthetic Agents,Anesthetic Drugs,Anesthetic Effect,Anesthetic Effects,Agents, Anesthetic,Drugs, Anesthetic,Effect, Anesthetic,Effects, Anesthetic
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia