Key result
Analytical modeling reveals IK1 largely dictates the critical inward current required for cardiac action potentials.
This computational study provides analytical expressions linking specific ion channel properties to tissue-scale processes like focal excitation and propagation, offering insights into the initiation of cardiac arrhythmias.
I(K1) may shape excitation thresholds in models; leaves open validation and arrhythmia relevance in vivo.
It is well known that a variety of cardiac arrhythmias are initiated by a focal excitation in heart tissue. At the single cell level these currents are typically induced by intracellular processes such as spontaneous calcium release (SCR). However, it is not understood how the size and morphology of these focal excitations are related to the electrophysiological properties of cardiac cells. In this paper a detailed physiologically based ionic model is analyzed by projecting the excitation dynamics to a reduced one-dimensional parameter space. Based on this analysis we show that the inward current required for an excitation to occur is largely dictated by the voltage dependence of the inward rectifier potassium current (I(K1)), and is insensitive to the detailed properties of the sodium current. We derive an analytical expression relating the size of a stimulus and the critical current required to induce a propagating action potential (AP), and argue that this relationship determines the necessary number of cells that must undergo SCR in order to induce ectopic activity in cardiac tissue. Finally, we show that, once a focal excitation begins to propagate, its propagation characteristics, such as the conduction velocity and the critical radius for propagation, are largely determined by the sodium and gap junction currents with a substantially lesser effect due to repolarizing potassium currents. These results reveal the relationship between ion channel properties and important tissue scale processes such as excitation and propagation.
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Greene et al. (2015) studied Cardiac arrhythmias. Analytical modeling of cardiac tissue excitation reveals that the critical inward current required for an action potential is largely dictated by the inward rectifier potassium current (I(K1)).
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