Zn²⁺ blocks the GABA-induced current via a noncompetitive mechanism. A, GABA (1 mm) was applied for 100 msec either alone (control) or in combination with different Zn²⁺ concentrations (as indicated).B, From eight nucleated patches a semilogarithmical dose–response curve for the Zn²⁺ block was constructed for the peak current and the slow component, respectively. In both curves, each point represents one to eight agonist applications. C, Different GABA concentrations (as indicated) were applied for 100 msec in the presence of 100 μm Zn²⁺ to the same nucleated patch to study the mechanism of blockade. GABA (1 mm) was first applied without Zn²⁺ as control. D, A semilogarithmical dose–response curve for GABA in the presence of Zn²⁺ was constructed from eight nucleated patches showing the noncompetitive mechanism of block. The peak currents (I_GABA) were normalized with respect to the response activated by 1 mm GABA alone. Although the EC₅₀ was not changed significantly in comparison to GABA alone, the I_max was reduced to 19% of the original value (see dashed control dose–response relationship taken from Fig. 2B). Note the calibration of the y-axis. Application of 1, 3, and 10 mm GABA yielded significantly smaller responses in combination with 100 μm Zn²⁺ than without (*, one-way ANOVA; p < 0.01). Eachpoint represents four to eight experiments.