Electrophysiological Mechanisms Underlying Rate-Dependent Changes of Refractoriness in Normal and Segmentally Depressed Canine Purkinje Fibers: The Characteristics of Post-Repolarization Refractoriness

Tissues from diseased hearts are known to exhibit post-repolarization refractoriness and rate-dependent changes of the refractory period that are often inconsistent with changes in action potential duration. To examine the electrophysiological mechanisms responsible for such rate-dependent changes of the refractory period, a narrow inexcitable zone was created by superfusing the central segments of Purkinje fibers with an ‘ion-free isotonic sucrose solution’. The degree of conduction impairment could be finely regulated by varying the resistance of the extracellular shunt pathway. At intermediate or low levels of block, the refractory period remained unchanged or decreased, respectively, as the rate was increased. At relatively high levels of block, however, we observed marked increases of the refractory period in response to increases in the stimulation rate. The disparity of refractoriness between normally conducting fibers and fibers exhibiting discontinuous conduction characteristics and post-repolarization refractoriness increased dramatically as a function of increasing stimulation rate. With the aid of current clamp techniques, we demonstrate that the differential behavior is due to the interplay between ratedependent changes (1) in the restitution of excitability at the site beyond the depressed zone secondary to changes in passive and active membrane properties and (2) in the intensity of local circuit current provided to that site by activity generated in the segment proximal to the zone of block. Our data suggest that rate-dependent changes of refractoriness in Purkinje tissue are principally governed by attendant changes in membrane resistance.