Further studies on the influence of cyclic nucleotides on junctional permeability in heart

The influence of cAMP on the cell-to-cell diffusion of Lucifer Yellow CH in heart muscle was further investigated. It was found that isoproterenol (10(-5) M) enhanced the diffusion coefficient (D) from 4 +/- 0.63 X 10(-7) cm2/s (control) to 2.4 +/- 0.66 X 10(-6) cm2/s. Dibutyryl-cAMP (5 X 10(-4) M) plus theophylline (0.4 mM) also increased the cell-to-cell diffusion of Lucifer Yellow CH (D = 3.2 +/- 0.69 X 10(-6) cm2/s). The effect of dBcAMP was increased by theophylline. Since the permeability of the surface cell membrane to the dye is negligible in presence of these drugs and the binding of Lucifer Yellow CH to cytoplasmic proteins was not altered, it is thus concluded that the enhanced longitudinal diffusion of the dye was due to an increase in junctional permeability. As the enhanced cell-to-cell diffusion of the dye caused by isoproterenol was quickly reversed the hypothesis of a greater synthesis of intercellular channels seems unlikely. Acetylcholine (10(-5) M) that increases the intercellular concentration of cGMP had no effect on cell-to-cell diffusion of the dye. The present results support the view that cAMP is a modulator of junctional permeability in heart muscle.