COMPARISON OF ACTIVATION OF NONSELECTIVE CATION CHANNELS BY PROTEIN KINASE-A IN GUINEA-PIG AND MOUSE PANCREATIC ACINAR-CELLS

The effects of cyclic AMP-dependent kinase (PKA) on non-selective cati on channels in the plasma membrane of guinea-pig and mouse pancreatic acinar cells were studied by patch-clamp single-channel techniques. In both species, ATP (1.4 mM) acting on the inside of the membrane (Ca2 concentration, 10(-6) M) inhibited the opening of the NSC channel wit h a unit conductance of 25 pS. The addition of a catalytic unit of PKA (25 U/ml) in the presence of ATP to the inside of guinea-pig cells ev oked an opening of a new channel, which is a Ca2+-activated and voltag e-sensitive NSC channel with a unit conductance of about 45 pS (in sym metrical monovalent cation-rich solution). On the other hand, 25 pS Ca 2+-activated NSC channet in mouse cells was re-opened by identical PKA application. The application of PKA-inhibitor did not activate NSC ch annels in either species. The addition of 10(-6) M ACh to the bath sol ution containing 10(-6) M insulin, whose addition with ACh has been re ported to increase cAMP, evoked a marked and sustained increase in the opening of the guinea-pig 45 pS or the mouse 25 pS NSC channel in int act cells (cell-attached configurations). This was not seen in the abs ence of insulin. These results suggest that the cAMP-dependent mechani sm in the pancreatic acinar cells can activate NSC channels in the pre sence of ATP on the inside of the cell.