Currents activated by GABA and their modulation by Zn2+ in cerebellar granule cells in culture. 1993

G Kilić, and O Moran, and E Cherubini
Scuola Internazionale Superiore di Studi Avanzati, Trieste, Italy.

Whole-cell and single-channel currents evoked by gamma-aminobutyric acid (GABA) were recorded from rat cerebellar granule cells in culture. The electrophysiological properties of these currents were studied in control condition and in the presence of external Zn2+ (10-30 microM). GABA (10 microM) induced bicuculline-sensitive whole-cell currents which desensitized. The desensitization was more rapid for higher concentrations of GABA (30-300 microM). The current-voltage relation of GABA currents was linear from -70 to +50 mV. Two different types of cells were found with respect to the stoichiometry for agonist binding, one with Hill coefficient 1.5 and another one with coefficient 1. The half-maximum concentration displayed more variability, with values varying from 10 to 50 microM. The time constant of recovery from desensitization (tau r) was estimated to be 36 s. Zn2+ (30 microM) blocked GABA-activated whole-cell currents in a non-competitive and voltage-independent way without a significant change in the current kinetics. In excised outside-out patches, GABA (0.5 microM) activated single-channel events of 19 and 31 pS. Kinetic analysis yielded two mean shut times (tau c1 = 2.70 ms, tau c2 = 205 ms) and one mean open time (tau o = 3.64 ms). Zn2+ (10 microM) did not affect single-channel conductances and mean open and shut times, but significantly reduced the probability of opening from 0.17 to 0.06. It is probable that Zn2+ binds to a site located on the extracellular part of the GABAA receptor channel complex.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D002531 Cerebellum The part of brain that lies behind the BRAIN STEM in the posterior base of skull (CRANIAL FOSSA, POSTERIOR). It is also known as the "little brain" with convolutions similar to those of CEREBRAL CORTEX, inner white matter, and deep cerebellar nuclei. Its function is to coordinate voluntary movements, maintain balance, and learn motor skills. Cerebella,Corpus Cerebelli,Parencephalon,Cerebellums,Parencephalons
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
D004553 Electric Conductivity The ability of a substrate to allow the passage of ELECTRONS. Electrical Conductivity,Conductivity, Electric,Conductivity, Electrical
D005680 gamma-Aminobutyric Acid The most common inhibitory neurotransmitter in the central nervous system. 4-Aminobutyric Acid,GABA,4-Aminobutanoic Acid,Aminalon,Aminalone,Gammalon,Lithium GABA,gamma-Aminobutyric Acid, Calcium Salt (2:1),gamma-Aminobutyric Acid, Hydrochloride,gamma-Aminobutyric Acid, Monolithium Salt,gamma-Aminobutyric Acid, Monosodium Salt,gamma-Aminobutyric Acid, Zinc Salt (2:1),4 Aminobutanoic Acid,4 Aminobutyric Acid,Acid, Hydrochloride gamma-Aminobutyric,GABA, Lithium,Hydrochloride gamma-Aminobutyric Acid,gamma Aminobutyric Acid,gamma Aminobutyric Acid, Hydrochloride,gamma Aminobutyric Acid, Monolithium Salt,gamma Aminobutyric Acid, Monosodium Salt
D006098 Granulocytes Leukocytes with abundant granules in the cytoplasm. They are divided into three groups according to the staining properties of the granules: neutrophilic, eosinophilic, and basophilic. Mature granulocytes are the NEUTROPHILS; EOSINOPHILS; and BASOPHILS. Granulocyte
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
D001569 Benzodiazepines A group of two-ring heterocyclic compounds consisting of a benzene ring fused to a diazepine ring. Benzodiazepine,Benzodiazepine Compounds
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor

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