Gap junction uncoupling and discontinuous propagation in the heart. A comparison of experimental data with computer...

The effects of octanol on longitudinal propagation in guinea pig papillary muscles were measured by intracellular microelectrodes. These data were compared with alterations in conduction induced by stepwise removal of gap junction channels in computer simulations of propagation based on a discontinuous cable model. Octanol reduced the velocity (theta) of propagating action potentials (APs) from 53.2 +/- 3.5 to less than 6.6 +/- 2.1 cm/s before block occurred. The maximal rate of rise (Vmax) changed in a biphasic manner, increasing from 133.1 +/- 5.4 in controls to 201.7 +/- 11.0 V/s when theta was 20.5 +/- 2.8 cm/s, and then declining to less than 58.6 +/- 15.2 V/s just before block. The input resistance and time constant of the AP foot increased, and the ascending limb of phase-plane loops became increasingly nonlinear and notched during octanol treatment. All effects of octanol reversed upon washout. A strand of cardiac tissue was modeled as a discontinuous cable composed of 40 cells, each with 10 isopotential membrane segments described by Beeler-Reuter kinetics, and coupled by a variable number of gap junction channels (156 pS). Decreasing the number of channels from 40,000 to 400 to 60 slowed conduction from 62.6 to 16.4 to 3.1 cm/s. As noted in the experimental data, Vmax increased from 103 to 130 and then fell to less than 96 V/s. The AP foot increased and became nonexponential. Distinct notches developed during phase 1 of the APs at slower propagation velocities in the experiments and simulations. The close similarities between the experimental and theoretical data obtained in this study supports the applicability of a discontinuous cable model for describing longitudinal propagation in the heart.