Quantitative contributions of individual ionic currents to AP rate dependence.

<p>(<b>A</b>) Hypothetical APs before (solid) and after a perturbation that causes RRD prolongation of the AP. (<b>B</b>) A specific hypothetical ionic current under the conditions shown in (<b>A</b>). This inward (i.e. depolarizing) current increases with the perturbation at the slow rate (gray shaded area) but barely changes at the fast rate (blue shaded area). (<b>C</b>) ΔQ is the integral of the difference in current between control and perturbation (shaded areas in (<b>B</b>)) in units of pC/nF. The large, negative ΔQ at slow pacing (gray bar) indicates that this current will prolong the AP at this rate, whereas the small, negative ΔQ at fast pacing (blue bar) indicates a minimal alteration of the AP at this rate. This current will therefore contribute to RRD AP prolongation. <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003543#pcbi.1003543.s004" target="_blank">Figure S4</a> shows additional hypothetical examples of ΔQ that can contribute to either RRD or FRD behavior.