Model & data sources
What do these terms mean?
Cell model & protocol
O'Hara–Rudy / ORd-CiPA is a mathematical model of a single human heart-muscle cell, built from real patch-clamp measurements. It doesn't simulate a whole heart — it solves the equations for one cell's electrical cycle, many times over.
- Endo / Epi / Mid
- the three layers of the ventricular wall (inner, outer, middle). Cells differ between them — see the Transmural heterogeneity panel.
- Cycle length
- time between simulated heartbeats. 2000 ms is a deliberately slow 30 bpm, the FDA's own CiPA protocol.
- Pre-paced beats
- the simulation runs 400 beats before recording, so the cell settles into its steady rhythm instead of being captured mid-"warm-up".
hERG & drug binding
hERG is a potassium channel gene; it's the single most common place a drug accidentally causes dangerous heart rhythms, because blocking it slows the heart's electrical "reset" between beats.
A Markov binding model describes how a drug molecule attaches to and detaches from hERG over time. Some drugs bind and release quickly; others get briefly "trapped" inside the channel, which is the more dangerous pattern.
Ion channels (INa, ICaL, Ito…)
Each channel is a separate "gate" in the cell membrane that lets one type of ion flow in or out. Together they draw the action-potential shape in the chart above.
- INa
- fast sodium — the initial spike of each beat.
- INaL
- late sodium — a small lingering leak; if it doesn't fade, the cell stays activated too long.
- ICaL
- L-type calcium — shapes the plateau and triggers the muscle to actually contract.
- Ito
- transient outward potassium — the brief early "notch" right after the spike.
- IKr / IKs
- rapid/slow delayed-rectifier potassium — the main "reset" currents; hERG encodes IKr.
- IK1
- inward-rectifier potassium — holds the cell at rest between beats.
qNet & ΔAPD90 (the metrics)
- qNet
- the net electrical charge moved across the membrane by six currents over one beat. The single number this project uses to predict risk — more negative means more risk.
- APD90
- how long the cell stays electrically activated before 90% resetting. A prolonged APD90 is the classic early-warning sign of risk, though a less reliable predictor than qNet (shown elsewhere on this page).
- FDA CiPA
- the FDA's Comprehensive in vitro Proarrhythmia Assay initiative — the regulatory framework this whole simulation implements.