Electrical uncoupling and impulse propagation in isolated sheep Purkinje fibers
Jalife, J.; Sicouri, S.; Delmar, M.; Michaels, D.C.
American Journal of Physiology 257(1 Pt 2): H179-H189
1989
ISSN/ISBN: 0002-9513 PMID: 2750935 Document Number: 342284
Alterations in electrical coupling may have a major role in the development of cardiac rhythm and conduction disturbances. We have used microelectrodes and linear Purkinje fibers to analyze the relative importance of cell-to-cell coupling on action potential propagation and to study the changes in the relationship between conduction velocity (.theta.) and upstroke velocity (Vmax) induced by three agents (heptanol, hypertonic solution, and ouabain) known to alter gap junction resistance. Heptanol superfusion (1.5-3.0 mM) reversibly led to a major decrease in .theta. and ultimately to block at a time when Vmax had been reduced by .apprx. 38%. Conduction delay was closely correlated with an increase in intracellular resistance (Ri), calculated as the sum of myoplasmic and junctional resistances, assuming a one-dimensional cable model. Qualitatively similar results were obtained by superfusion with 0.1-0.5 mM ouabain or hypertonic Tyrode solution (up to 600 mM sucrose added) instead of heptanol. In contrast, when the Vmax vs. .theta. relationship was studied by changing the KCl from 4 to 20 mM, decreases in Vmax correlated well with changes in .theta. No significant effects on Ri were observed during KCl superinfusion. Finally, we developed a computer model of action potential propagation along a one-dimensional strand of 90 electrically coupled heart cells. By changing systematically the degree of electrical coupling or the maximum sodium conductance in the model and by studying the effects of these changes on propagation and Vmax, we obtained strong evidence supporting the validity of our experimental results. The overall data provide testable predictions regarding the role of electrical uncoupling on abnormal impulse propagation.