Currents Activated by GABA and their Modulation by Zn²⁺ in Cerebellar Granule Cells in Culture

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 Zn²⁺ (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. Zn²⁺ (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). Zn²⁺ (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 Zn²⁺ binds to a site located on the extracellular part of the GABA_A receptor channel complex.