Table I.

Model systems for evaluating biological pacemaker channels

	In Vivo	In Vitro	In Silico
Pro	Most predictive of therapeutic outcome, particularly when large animal models are employed	Suitable for detailed biophysical characterization; can obtain both rate and rhythm information when employing a myocyte culture	Fastest and most economical means to compare different biophysical properties; can provide insight into which channel parameters are most useful to modify
Con	Expensive and time consuming if comparing many channel constructs	Removed from intact animal situation; rate and rhythm information still fairly time consuming to acquire; ideally should employ localized expression, which is more difficult	Highly dependent on accuracy of the model, particularly regarding non-equilibrium behavior of expressed channel; also dependent on accurate biophysical data from in vitro studies