Endogenous protein phosphatase 1 runs down gap junctional communication ofrat ventricular myocytes

Gap junctional channels are essential for normal cardiac impulse propagatio n. In ventricular myocytes of newborn rats, channel opening requires the pr esence of ATP to allow protein kinase activities; otherwise, channels are r apidly deactivated by the action of endogenous protein phosphatases (PPs). The lack of influence of Mg2+ and of selective PP2B inhibition is not in fa vor of the involvements of Mg2+ dependent PP2C and PP2B, respectively, in t he loss of channel activity. Okadaic acid (1 muM) and calyculin A (100 nM), both inhibitors of PP1 and PP2A activities, significantly retarded the los s of channel activity. However, a better preservation was obtained in the p resence of selective PP1 inhibitors heparin (100 mug/ml) or protein phospha tase inhibitor 2 (I2; 100 nM). Conversely, the stimulation of endogenous PP 1 activity by p-nitrophenyl phosphate, in the presence of ATP, led to a pro gressive fading of junctional currents unless I2 was simultaneously added. Together, these results suggest that a basal phosphorylation-dephosphorylat ion turnover regulates gap junctional communication which is rapidly deacti vated by PP1 activity when the phosphorylation pathway is hindered.