Reconstruction of the repolarization process in cardiac Purkinje fibres based on voltage clamp measurements of membrane current.

1. The results of the voltage clamp experiments described in a preceding paper (Noble & Tsien, 1969) have been used to reconstruct the repolarization process in Purkinje fibres.2. The results show that, at the beginning of the plateau, the instantaneous current-voltage relation has a region of net inward current which, in the absence of additional outward current, would prevent repolarization.3. The activation of the outward current, i(x1), overcomes this region of inward current within about 300 msec. This first phase of the plateau is limited mainly by the speed of activation of i(x1) and, during this time, there exists a threshold for all-or-nothing repolarization. The calculated time course of this threshold corresponds well with that recorded experimentally in uniformly polarized preparations.4. Once the net inward current has been abolished, the rate of repolarization is mainly limited by the membrane capacity, although i(x1) continues to activate until about 500 msec. The outward current, i(x1), begins to deactivate during the rapid terminal phase of repolarization, but it is not fully deactivated at the end of the action potential. A second action potential initiated at this time would therefore be shorter than the first.5. The effect of the initial outward current transient, recently identified as largely chloride current (Dudel Peper, Rüdel & Trautwein, 1967 a), has been calculated. The result is a notch at the beginning of the plateau similar to that often recorded experimentally. The action potential duration is not greatly influenced by this current component.6. The role of outward currents other than i(x1) in repolarization is discussed. It is concluded that the outward current component primarily responsible for terminating the action potential may vary and depends on the action potential duration. In Purkinje fibres with action potentials of normal duration, i(x1) is the main time-dependent outward current involved.