Intracellular cyclic AMP concentration modulates gap junction permeability in parturient rat myometrium

We investigated whether cell-to-cell coupling between myometrial cells of parturient rats is influenced by intracellular adenosine 3',5'-cyclic monophosphate (cAMP) concentration. To evaluate the coupling, we measured input resistance (Ro) and injected Lucifer Yellow (LY) using microelectrode techniques. The intercellular spread of the dye was then observed. Longitudinal muscle strips from rat myometrium were exposed to isoproterenol, forskolin, or dibutyryl cAMP (DB-cAMP) to elevate cAMP. Isoproterenol (10(-11)-10(-6) M) and DB-cAMP (10(-5)-10(-3) M) hyperpolarized the resting membrane potential (Em) and increased Ro in a dose-dependent fashion. Forskolin (10(-6) M) also hyperpolarized Em and increased Ro. When LY was injected into a single cell, LY spread rapidly and extensively to neighboring cells in parturient control tissues, while LY transfer was completely blocked by any of the three agents at high concentrations. The increased Ro and blocked transfer of LY owing to these agents indicate that the cell-to-cell coupling was decreased both electrically and metabolically. Myometrial cells of parturient rats show increased number and size of gap junctions (GJs). The rapid and reversible decrease in coupling is interpreted to reflect the reduced permeability of GJs between the muscle cells because of an elevation of cAMP. Control of GJ permeability by this second messenger may be important for the physiological regulation of intercellular coupling and the extent of synchronizing and coordinating electrical, metabolic, and contractile activity in the uterine wall during pregnancy and parturition.