Sensitization of Ca(2+)-dependent K(+)-channels in Guinea-pig pancreatic acinar cells by phosphorylation.

The effects of adenosine 3', 5'-cyclic monophosphate (cAMP)-dependent protein phosphorylation on Ca(2+)-sensitivity of Ca(2+)-dependent K(+)-channels in guinea-pig pancreatic acinar cells were studied by patch-clamp single-channel methods. When opening of the channels did not occur in excised inside-out membrane patches exposed to 10(-6) M Ca2+, the addition of 25 U/ml catalytic units of cAMP-dependent protein kinase (PKA) to the bath solution opened the channels, with a conductance of 30 pS (in symmetrical K(+)-rich solution). The addition of a PKA-inhibitor (100 microM) extinguished the PKA-dependent opening of the K(+)-channels. Alkaline phosphatase (5 U/ml) reversed the PKA-dependent opening of the K(+)-channels to control levels (before PKA). These results demonstrate that cAMP-dependent protein phosphorylation initiates the Ca(2+)-sensitivity of the Ca(2+)-dependent K(+)-channels in guinea-pig pancreatic acinar cells.