Figure 6.

SynII(−) inhibitory synapses have reduced sensitivity to Ca²⁺ channel blockade by Cd²⁺, as well as a reduced ability to respond to Ca²⁺ elevation. A, Representative IPSC recordings obtained in 5 mm extracellular Ca²⁺ and different Cd²⁺ concentrations (red represents no cadmium; green represents 5 μm; blue represents 50 μm). Each trace is the average of 50 sweeps recorded in the same experiment. B, Cd²⁺ titration of inhibitory transmission demonstrates that WT GABAergic synapses have a stronger facilitation by elevated Ca²⁺ than SynII(−) synapses. In WT synapses, IPSC amplitudes are increased at elevated Ca²⁺ and low (<2 μm) Cd²⁺ concentrations (p = 0.04, n = 6 per two-way ANOVA), whereas higher Cd²⁺ concentrations abolish this difference. The stimulation intensity was adjusted to evoke similar responses in both lines at normal Ca²⁺ levels (2.5 mm Ca²⁺). Data collected from 3 WT and 3 SynII(−) presymptomatic mice (2 cell for each animal, 50 sweeps) were recorded at each Ca²⁺ and Cd²⁺ concentration. C, Fit to the data presented in the B by the Hill function. K₅₀ is significantly higher in SynII(−) synapses (p = 0.035).