We studied the role of Ca2+ diffusion through gap junctions (GJs) in triggering trod propagation of damage induced contractions in cardiac muscle (TPCs) by evaluating effects of the GJ blockers octanol and heptanol (O and 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 [Ca2+](o). Force was measured with a silicon strain gauge; sarcomere length, by laser diffraction techniques O and 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 and 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 and 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 and 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 μm2/s, which decreased to 12.6±1.5 and 7.07±0.7 μm2/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 Ca2+-induced Ca2+ release mediated by Ca2+ 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 and H slow triggering of TPCs, presumably by blocking Ca2+ diffusion from myocytes within damaged areas to adjacent normal cells.
- gap junction
- rat cardiac trabecula
- triggered propagated contraction