Slow inward current may produce many results attributed to IX1 in cardiac Purkinje fibers.

We have tried to answer two fundamental questions concerning the outward current IX1 of cardiac Purkinje fibers. 1) Is it possible that current changes identified as arising from IX1 in voltage-clamp experiments are actually manifestations of changes in the slow inward current (Isi); and 2) is IX1 in fact required to produce the electrical phenomena attributed to it? Isi behavior and the role of IX1 were explored using computer simulation. The Isi model produced current changes during depolarizations and hyperpolarizations from depolarized resting potentials like those attributed to IX1. It also produced a component of "tail currents" that behaved like IX1. If these current changes were analyzed, assuming that an outward current is responsible, the resulting kinetics and current voltage relation would be very similar to the kinetics and current voltage relation reported for IX1. Using the McAllister, Noble, and Tsien formulation of the Purkinje fiber action potential, we found that IX1 is not essential for repolarization of the reconstructed action potential nor is it needed to reproduce interval duration effects and the effects of applied current in that model. Data suggesting that calcium channel blockers reduce IX1 and that catecholamines increase IX1 may be explained as arising from changes in Isi. Thus many manifestations of IX1 can be explained as arising from unanticipated behavior of Isi, and IX1 does not necessarily play a key role in generating Purkinje fiber electrical activity.