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Currents Activated by GABA and their Modulation by Zn 2+ in Cerebellar Granule Cells in Culture
Author(s) -
Kilic Gordan,
Moran Oscar,
Cherubini Enrico
Publication year - 1993
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.1993.tb00206.x
Subject(s) - chemistry , biophysics , extracellular , bicuculline , granule (geology) , patch clamp , gamma aminobutyric acid , gabaa receptor , aminobutyric acid , agonist , kinetics , analytical chemistry (journal) , receptor , biochemistry , chromatography , physics , biology , quantum mechanics , paleontology
Whole‐cell and single‐channel currents evoked by γ‐aminobutyric acid (GABA) were recorded from rat cerebellar granule cells in culture. The electro‐physiological properties of these currents were studied in control condition and in the presence of external Zn 2+ (10 – 30μM). GABA (10 μM) induced bicuculline‐sensitive whole‐cell currents which desensitized. The desensitization was more rapid for higher concentrations of GABA (30 – 300 μM). 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 μM. The time constant of recovery from desensitization (T r ) was estimated to be 36 s. Zn 2+ (30 μM) 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 μM) activated single‐channel events of 19 and 31 pS. Kinetic analysis yielded two mean shut times (T c1 = 2.70 ms, T c2 = 205 ms) and one mean open time (T o = 3.64 ms). Zn 2+ (10 μM) 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 Zn 2+ binds to a site located on the extracellular part of the GABA A receptor channel complex.