Figure 3.

Example of the use of computational systems biology to model a genetic buffering mechanism. (a) Membrane potential variations in a model of the sinus node pacemaker of the heart. (b) The background sodium channel, i_b,Na, is progressively reduced until it is eventually ‘knocked out’. (c) The mixed (sodium and potassium) cation current channel, i_f, progressively takes over the function, and so ensures that the change in frequency is minimized (adapted from Noble et al. [61]), recomputed using COR: http://cor.physiol.ox.ac.uk/. Coordinates: membrane potential in millivolt, current in nanoampere, time (abscissa) in milliseconds.