Table 1 Experimentally observed changes in current density associated with cAF are well predicted by POMs calibrated to distributions.

Experimentally observed changes in current density associated with cAF are well predicted by POMs calibrated to distributions.. Changes in median current activities between the POMs calibrated to either the distributions or the ranges of the SR and cAF data sets, as compared with experimentally observed (Exp.) measurements of changes in current densities associated with this pathology. Experimental figures are taken from the specified references and rounded to the closest 10% to reflect the general uncertainty in their measurements and, in some cases, represent the combined result of multiple studies. The “↔” symbol indicates no significant change observed (P ≥ 0.01 from the Mann-Whitney U test for POMs). Distribution-calibrated POMs detect more of the differences in current densities that underlie the cAF pathology, correlating well with experimentally observed changes in the greatest majority of current densities.

ParameterExp.POMs (distributions)POMs (ranges)
gNa↕* (66)+11%
gto~−70% (37)−85%−51%
gKur~−50% (37)−40%−6%
gKr (31)+10%
gKs~+100% (41)
gK1~+100% (37)+29%+33%
gCaL~−70% (37, 67)−36%
INaK(max)↔ (68)+10%
INaCa(max)~+40% (40)+41%−18%
Iup(max) (42, 43)−39%
krel§ (42)

*Peak INa current is reduced, but sustained INa increased.

†Decreases in mRNA levels have been observed (37), but no direct experimental evidence for change in cAF has yet been provided.

‡Ca2+ uptake is reduced by decreased Serca2a levels but increased by enhanced phosphorylation of SERCA inhibitors.

§Ca2+ release is increased but in a “leaky” fashion not necessarily best represented by changes to krel in the CRN model.