During control superfusion with oxygenated normal Ty-rode’s solution, the intracellularly injected dye spread widely to the neighbouring cells (Figure 1, top), exhibiting good intercellular coupling. When Ca2+ concentration of the Tyrode’s solution was elevated to 6 mM or the solution was made hypoxic, the intracellularly injected dye remained confined within the injected cell, and was not observed to spread to the surrounding cells (Figure 1, middle). Lack of spread of fluoresceine dye indicated, in both cases, failure of intercellular coupling. With addition of 0.1 or 0.5 |JM tedisamil to either high Ca2+ or hypoxic solution, wide spreading of the dye was observed (Figure 1, bottom), as during control superfusion. These results showed that tedisamil prevents the decoupling caused by either high Ca2+ concentration or hypoxia and markedly increases intercellular coupling.
Figure 1 Demonstration of intercellular spreading of Lucifer yellow CH in right ventricular muscle preparation from guinea pig heart. Top Many cells can be seen to fluoresce following superfusion of tissue with oxygenated normal Tyrode’s solution. Middle Following superfusion with high Ca2+ concentration (6mM) Tyrode’s solution, the fluorescent dye did not spread from the injected cell. Bottom Following addition of 0.5 fiM tedisamil to the high Ca Tyrode’s solution, spreading of the fluorescent dye was evident. Calibration bar: 100 fim
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