1-Heptanol is known to uncouple gap junctions and has been used previously to study the electrical consequences of the disruption of cell-cell coupling in heart muscle. In this study, the effects of 1-Heptanol on restitution and dispersion of monophasic action potential (MAP) duration, and on activation (conduction) delay was studied in isolated rabbit hearts. Direct effects on E-C coupling were examined by measuring intracellular [Ca²⁺] and cell shortening in isolated cells. Hearts were removed from terminally anaesthetised rabbits (100 mg kg^-1 Euthatal) and perfused (Langendorff mode) with Krebs-Henseleit solution (37 °C). Electrical recordings were obtained from the epicardial surface of the left ventricle (LV) using a latex jacket containing 32 MAP electrodes. The protocol involved stimulating the heart, via bipolar electrodes, with 8 or 16 basic S1 beats at 350 ms intervals followed by an extra stimulus S2 and a 1000 ms pause. S1-S2 was progressively increased from 70 to 600 ms. S1-S2 changes of 5 ms were made between 70 and 150 ms, 10 ms between 150 and 350 ms, and 50 ms between 350 and 600 ms. Protocols were run initially in Tyrode solution, then after addition of 0.3 mM 1-Heptanol. Activation delay was prolonged with 1-Heptanol from 50.9 ± 0.9 to 58.1 ± 1.0 ms (mean ± S.E.M.) (Student’s t test, P < 0.05, n = 17). LV MAPs from the last S1 in the 8 or 16 beat train and from S2 were analysed at 90 % repolarisation (MAPD₉₀). In ~50 % of cases S2 MAPD₉₀ increased with S1-S2 intervals up to a local maximum at ~180 ms but decreased at longer intervals (350 ms). The remainder of cases showed a typical electrical restitution curve with no negative slope. In Tyrode solution the gradient of the slope was -0.035 ± 0.004, while in 0.3 mM 1-Heptanol the gradient of the slope was -0.048 ± 0.040 (P < 0.05, n = 17). Dispersion of repolarisation showed a slight but non-significant increase in the presence of 0.3 mM 1-Heptanol. The increased activation delay and dispersion of repolarisation in the presence of 1-Heptanol are expected consequences of cell-cell uncoupling. However, the biphasic relationship in the restitution curve may result directly from an effect on sarcolemmal channels or indirectly by modifying other aspects of E-C coupling. Preliminary data on isolated cells indicate the 1-Heptanol reduced peak systolic Ca²⁺ in isolated sub-epicardial cells. The subcellular basis for this effect is unknown, but the results suggest that 1-Heptanol does not simply disrupt cell-cell electrical coupling.

This research was supported by MRC and BHF.