Page 152 - Visions of the Future Chemistry and Life Science

Figure 8.1. Scheme of a ventricular action potential (a) and its sub-cellular mechanisms (b). Membrane potential models simulate
action potentials (a) with a deliberately small number of equations; ionic current models reproduce the action potential on the basis
of calculating the sub-cellular ion movements that actually give rise to it (b). (a) Cardiac contraction is controlled by an electrical
waveform called action potential. Action potentials are induced by change in cell voltage to less negative values. Cells are said to
‘depolarise’ from their resting potential (RP) towards a threshold (Thr), at which automatic excitation occurs: an action potential is
initiated. The action potential is characterised by a swift upstroke to positive cell voltages, followed by a plateau and slower return
to RP levels. The well-ordered spread of this waveform provides the basis to the regular contraction of the heart. (b) Example of
major constituent parts of a detailed ionic current model (here Oxsoft Heart v4.8). The model incorporates essential intracellular
structures like the contractile proteins, sarcoplasmic reticulum (SR, a calcium store) or mitochondria (MX, the powerhouse of the
cell). It computes the action potential as a function of ion movements through channels (see a selection, top left), exchangers and
pumps (bottom). This makes it possible to predict the cell’s electrical and mechanical activity, and to account for effects of receptor
stimulation (see selection at top right: adrenergic – , and cholinergic receptors – M , that provide neural input), or changes in
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substrate transporter activity, cell metabolism and pH (right hand side). With this type of models, (patho-) physiological behaviour
may be simulated as it develops in time. From Kohl et al. 2000.