ABSTRACT
These scales are linked, because organ level function of the heart is an emergent product of events at the molecular scale. An example of these links that we will consider later is gene polymorphisms associated with altered function of the Na+ ion channel. These molecular level changes result in organ level phenomena including cardiac arrhythmias. However, the causal chain operates in both directions, and events at the tissue and organ scale also influence the behaviour of cells and molecules. For example, mechanical stress within the heart wall can open stretch activated ion channels, and so a tissue level effect influences molecular level processes. This bi-directional coupling across scales poses a problem for explaining heart function; should the explanation start with small scale (molecule and cell) detail and work upwards to describe the tissue and organ scales, or should it start with tissue and organ scale function and infer the underlying cellular and molecular mechanisms that are important? This issue of whether to take a ‘bottom-up’ or ‘top-down’ approach is a general problem in systems biology. A bottom-up approach relies on detailed and complete knowledge of small scale function, whereas a top-down approach does not guarantee a unique explanation.
