Conduction block in Purkinje fibers by homogeneous versus localized decrease of the gap junction conductance

Gap junction channels provide the pathway for the cell-to-cell propagation of cardiac action potential. Impairment of junctional conductance decreases conduction velocity and can cause block, two conditions that favor ventricular arrhythmias and fibrillation by re-entrant excitation. These experiments were designed to examine the effects of homogeneous versus localized decrease of the gap junction conductance on propagation of action potential in Purkinje fibers from sheep hearts. The fibers were mounted in a three-compartment chamber, and cell-to-cell conductance was progressively reduced by applying heptanol either over a central 2-mm segment or over the whole fiber length. The internal resistivities (Ri) at which conduction of the action potential became blocked were determined in both cases. With 3.5 mM heptanol in the central compartment, conduction failed when Ri was increased by only 3-4.6 times the control values. In contrast, when the same concentration of heptanol was added simultaneously to all three compartments, Ri had to rise by a factor of 7.5-9.4 before conduction became decremental and was blocked. In both situations, dV/dt(max) at the time of conduction block was similarly decreased to about 50% of the control values. Other parameters being equal, a moderate decrease of the gap junction conductance and of the fast sodium current, insufficient to block propagation of the action potential when they are homogeneously distributed, become sufficient to interrupt conduction if the action potential merges abruptly into a portion of fiber with normal internal conductivity at the outlet of the area of increased resistance. This greater sensitivity to block is accounted for by the increase in electrical load at the discontinuity in the core conductor between the region of increased internal resistance and the normal part of fiber that follows. Areas of steep transition from high to low input resistances of the core conductor, such as may develop in localized ischemia, therefore appear particularly susceptible to conduction failure.