Delayed rectification in the calf cardiac Purkinje fiber. Evidence for multiple state kinetics

We have investigated the delayed rectifier current (Ix) in the calf cardiac Purkinje fiber using a conventional two-microelectrode voltage clamp arrangement. The deactivation of Ix was monitored by studying decaying current tails after the application of depolarizing voltage prepulses. The reversal potential (Vrev) of these Ix tails was measured as a function of prepulse magnitude and duration to test for possible permeant ion accumulation- or depletion-induced changes in Vrev. We found that prepulse-induced changes in Vrev were less than 5 mV, provided that prepulse durations were less than or equal to 3.5 s and magnitudes were less than or equal to +35 mV. We kept voltage pulse structures within these limits for the remainder of the experiments in this study. We studied the sensitivity of Vrev to variation in extracellular K+. The reversal potential for Ix is well described by a Goldman-Hodgkin-Katz relation for a channel permeable to Na+ and K+ with PNa/PK = 0.02. The deactivation of Ix was always found to be biexponential and the two components shared a common reversal potential. These results suggest that it is not necessary to postulate the existence of two populations of channels to account for the time course of the Ix tails. Rather, our results can quantitatively be reproduced by a model in which the Ix channel can exist in three (two closed, one open) conformational states connected by voltage dependent rate constants.