Triggered Propagated Contractions in Rat Cardiac Trabeculae

Abstract

We studied the role of Ca 2+ diffusion through gap junctions (GJs) in triggering and propagation of damage-induced contractions in cardiac muscle (TPCs) by evaluating effects of the GJ blockers octanol and heptanol (O&H) on TPCs. TPCs were elicited in trabeculae from rat right ventricle superfused with Krebs-Henseleit solution at 20°C and 0.7 to 1.75 mmol/L [Ca 2+ ] o . Force was measured with a silicon strain gauge; sarcomere length, by laser diffraction techniques. O&H (3 to 300 μmol/L) decreased force, propagation velocity, and triggering rate of TPCs in a dose-dependent manner. At 300 μmol/L, O&H decreased TPC force to 21.3% and 25.7%, propagation velocity to 15.4% and 13.0%, and triggering rate to 26.5% and 25.7%. At 300 μmol/L, O&H decreased twitch force to 79.0% and 77.8% and reduced time to 90% relaxation by 10% to 15%. Above 1 mmol/L, O&H abolished twitch force and TPCs. Image analysis of spread of the fluorescence profile of microinjected fura 2 salt revealed an effective diffusion coefficient for fura 2 of 21.0±3.3 μm 2 /s, which decreased to 12.6±1.5 and 7.07±0.7 μm 2 /s after 1 and 3 hours of exposure, respectively, to 100 μmol/L octanol, with a time constant of decline of 1.5±0.5 hours. These results are consistent with the hypothesis that propagation of TPCs is due to Ca 2+ -induced Ca 2+ release mediated by Ca 2+ diffusion from cell to cell through GJs. Reduction of propagation velocity reduces the number of activated sarcomeres in the TPC, which reduces TPC force. O&H slow triggering of TPCs, presumably by blocking Ca 2+ diffusion from myocytes within damaged areas to adjacent normal cells.