Channelrhodospin-2 (ChR2), a light-sensitive ion channel, and its variants have 
emerged as new excitatory optogenetic tools not only in neuroscience, but also 
in other areas, including cardiac electrophysiology. An accurate quantitative 
model of ChR2 is necessary for in silico prediction of the response to optical 
stimulation in realistic tissue/organ settings. Such a model can guide the 
rational design of new ion channel functionality tailored to different cell 
types/tissues. Focusing on one of the most widely used ChR2 mutants (H134R) with 
enhanced current, we collected a comprehensive experimental data set of the 
response of this ion channel to different irradiances and voltages, and used 
these data to develop a model of ChR2 with empirically-derived voltage- and 
irradiance- dependence, where parameters were fine-tuned via simulated annealing 
optimization. This ChR2 model offers: 1) accurate inward rectification in the 
current-voltage response across irradiances; 2) empirically-derived voltage- and 
light-dependent kinetics (activation, deactivation and recovery from 
inactivation); and 3) accurate amplitude and morphology of the response across 
voltage and irradiance settings. Temperature-scaling factors (Q10) were derived 
and model kinetics was adjusted to physiological temperatures. Using optical 
action potential clamp, we experimentally validated model-predicted ChR2 
behavior in guinea pig ventricular myocytes. The model was then incorporated in 
a variety of cardiac myocytes, including human ventricular, atrial and Purkinje 
cell models. We demonstrate the ability of ChR2 to trigger action potentials in 
human cardiomyocytes at relatively low light levels, as well as the differential 
response of these cells to light, with the Purkinje cells being most easily 
excitable and ventricular cells requiring the highest irradiance at all pulse 
durations. This new experimentally-validated ChR2 model will facilitate virtual 
experimentation in neural and cardiac optogenetics at the cell and organ level 
and provide guidance for the development of in vivo tools.