Figure 4.

Progressive distortion of the Ca²⁺ transient during a train of glutamate pulses, in cells with severe mitochondrial dysfunction. (A) Overlays of the Ca²⁺ fluorescence in response to a single glutamate application and to a short train of applications in the parental cell line, ES-I. The single application (‘singlet’) response is duplicated and time shifted (black trace) to overlay the final response in the train. The final response in the train typically shows the same decay kinetics in control cell lines. These analyses were only performed for cells which showed identical initial responses (<2% variability). (B) Similar traces for Cy3-I, the cell line with a severe mitochondrial deficit. Note the marked deviation of the decay of the train relative to that of the singlet. (C) A ‘residual’ trace is calculated simply by subtracting the singlet response from the final response in the train. The example shows the derivation for the traces in panel B (Cy3-I line).