2.8 In silico model reconstruction
The O’Hara-Rudy (ORd) human ventricular model(O’Hara, Virág, Varró &
Rudy, 2011) was modified to incorporate the actions on multi-channel
block of HCQ, including the dose-dependent block of
INa,, ICaL,, Ito,
IKr, IKs IK1 and the
Na+-Ca2+ exchange current,
INCX. This model was selected as it was developed from
and validated against experimental data from human ventricular cells and
found suitable for studying actions of drugs. The simulations evoked
action potentials by a supra-threshold stimulus in control runs and
following application of HCQ, and combined application of HCQ and AZM.
Action potential time courses characterized by AP durations at 90%
repolarisation (APD90) and maximal upstroke velocity
(MUP) and the underlying ion channel currents targeted by the drugs were
recorded for analysis.