Cellular Interrogation: Exploiting Cell-to-Cell Variability to Discriminate Regulatory Mechanisms in Oscillatory Signalling
Fig 10
Gap detection with the AT1 model.
(A) Plots of cytoplasmic Ca2+ for three representative cells in three experiments in which a step increase in histamine was interrupted by two (expt. 21 & 23) or five (expt. 22) gaps, with the size of the gap changing between experiments as shown. The first two gaps are marked by a black diamond when the gap was detected, based on a manual scoring of any feature of the Ca2+ trajectory that showed a discernible change at the gap (S1 Text). The percentage of cells that detect the first gap steadily increases with gap size but cells 21-3, 21-8 and 22-171 are able to detect the second gap despite missing the first. (B) Plots of cytoplasmic Ca2+ (blue) and IP3 (black) for the AT1 model responding to a step increase in histamine interrupted by two gaps of 15 seconds. The initial Ca ER and the timescale for IP3 decay, τ, were chosen as shown (τ corresponds to ir−1 in S1 Text), with the other initial conditions and parameter values as in the original paper. As τ decreases below the gap duration, the second gap is detected when τ = 10 sec and then both gaps are detected when τ = 5 sec. (C) The middle simulation in B is repeated with initial Ca ER lowered from 19 μM to 15 μM and both gaps are then detected.