Endogenous protein phosphatase 1 runs down gap junctional communication of rat ventricular myocytes

Gap junctional channels areessential for normal cardiac impulse propagation. In ventricularmyocytes of newborn rats, channel opening requires the presence of ATPto allow protein kinase activities; otherwise, channels are rapidlydeactivated by the action of endogenous protein phosphatases (PPs). Thelack of influence of Mg²⁺ and of selective PP2B inhibitionis not in favor of the involvements of Mg²⁺-dependent PP2Cand PP2B, respectively, in the loss of channel activity. Okadaic acid(1 µM) and calyculin A (100 nM), both inhibitors of PP1 and PP2Aactivities, significantly retarded the loss of channel activity.However, a better preservation was obtained in the presence ofselective PP1 inhibitors heparin (100 µg/ml) or protein phosphataseinhibitor 2 (I2; 100 nM). Conversely, the stimulation of endogenous PP1activity by p-nitrophenyl phosphate, in the presence of ATP,led to a progressive fading of junctional currents unless I2 wassimultaneously added. Together, these results suggest that a basalphosphorylation-dephosphorylation turnover regulates gap junctionalcommunication which is rapidly deactivated by PP1 activity when thephosphorylation pathway is hindered.