Barbiturate-induced alterations in the kinetic parameters of slow outward current in Aplysia giant neurons. 1985

J R Huguenard, and W A Wilson

Regulation of spike frequency adaptation has been postulated to be a neuronal mechanism of action of the barbiturates (Zbicz and Wilson, 1981). A barbiturate sensitive slow outward current is present in Aplysia giant neurons, and this current is very effective at regulating adaptation. In the current study a quantitative method of determining the effect of barbiturates was developed using a single-electrode voltage clamp. This method, tail current analysis, involved measuring the exponential decay of the slow outward current at the end of a depolarizing voltage-clamp command. The tail currents were made up of two decay phases with average half-times of 7 and 70 sec, and the tail current amplitude accurately reflected the magnitude of slow outward current. Barbiturates were found to cause a concentration-related, saturable and stereospecific increase in one component of the tail currents, the amplitude of the slow phase. With moderate concentrations of barbiturates there were no changes in the other parameters describing the exponential decay current. The rank order of potency of barbiturates for the enhancement of slow outward current was not well correlated with the lipid solubility of these drugs, indicating that slow outward current enhancement is not due to a nonspecific mechanism, but rather may be receptor mediated.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
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
D010424 Pentobarbital A short-acting barbiturate that is effective as a sedative and hypnotic (but not as an anti-anxiety) agent and is usually given orally. It is prescribed more frequently for sleep induction than for sedation but, like similar agents, may lose its effectiveness by the second week of continued administration. (From AMA Drug Evaluations Annual, 1994, p236) Mebubarbital,Mebumal,Diabutal,Etaminal,Ethaminal,Nembutal,Pentobarbital Sodium,Pentobarbital, Monosodium Salt,Pentobarbitone,Sagatal,Monosodium Salt Pentobarbital
D010634 Phenobarbital A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations. Phenemal,Phenobarbitone,Phenylbarbital,Gardenal,Hysteps,Luminal,Phenobarbital Sodium,Phenobarbital, Monosodium Salt,Phenylethylbarbituric Acid,Acid, Phenylethylbarbituric,Monosodium Salt Phenobarbital,Sodium, Phenobarbital
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
D000200 Action Potentials Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli. Spike Potentials,Nerve Impulses,Action Potential,Impulse, Nerve,Impulses, Nerve,Nerve Impulse,Potential, Action,Potential, Spike,Potentials, Action,Potentials, Spike,Spike Potential
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
D001048 Aplysia An opisthobranch mollusk of the order Anaspidea. It is used frequently in studies of nervous system development because of its large identifiable neurons. Aplysiatoxin and its derivatives are not biosynthesized by Aplysia, but acquired by ingestion of Lyngbya (seaweed) species. Aplysias
D001463 Barbiturates A class of chemicals derived from barbituric acid or thiobarbituric acid. Many of these are GABA MODULATORS used as HYPNOTICS AND SEDATIVES, as ANESTHETICS, or as ANTICONVULSANTS.
D013237 Stereoisomerism The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed) Molecular Stereochemistry,Stereoisomers,Stereochemistry, Molecular,Stereoisomer

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