Reconstruction of transport currents during repolarization: biochemical basis

A philosophy and approach is described for including enzyme-mediated transport currents in reconstructions of ion regulation and electrical activity in cardiac muscle. Data from physiological and biochemical experiments on isolated transport systems are combined with the principles of physical chemistry to construct mechanistic descriptions of the systems. These descriptions are then combined (unmodified) together with the results of morphological measurements on cells to reconstruct the behavior of the ion regulation system. Some results from a preliminary model of this type are described: calcium regulation by the plasmalemma, including sodium-calcium exchange, the calcium pump (ATPase), and a calcium leak. This subsystem is stable at physiological values of ion concentrations and transmembrane potential and the net flux through the leak is within the range determined experimentally. Under these conditions, most of the calcium entering the cell through the leak is shown to be restored by the calcium pump. From calculations with an action potential of arbitrary waveform, it is shown that sodium-calcium exchange can make a small, but measurable contribution to repolarization in the cardiac cell.