DECREASE OF ACIDITY INSIDE ZYMOGEN GRANULES INHIBITS ACETYLCHOLINE-EVOKED OR INOSITOL TRISPHOSPHATE-EVOKED CYTOSOLIC CA2-CELLS( SPIKING IN PANCREATIC ACINAR)

In isolated pancreatic acinar cells application of the proton-potassiu m ionophore nigericin or the proton-sodium ionophore monensin led to a reduction of acidity inside the zymogen granules which could be visua lized in an imaging system by a rapid reduction in the intragranular q uinacrine fluorescence. Cytosolic Ca2+ spikes in response to acetylcho line stimulation or intracellular inositol trisphosphate application w ere assessed by recording Ca2+-sensitive ionic currents in the patch c lamp whole-cell recording configuration. Both nigericin and monensin e voked marked reductions in frequency and amplitude of spikes and in ma ny experiments abolished spiking altogether. The Ca2+-sensitive membra ne currents could still be activated after nigericin or monensin treat ment since subsequent application of the Ca2+ ionophore ionomycin evok ed a large current response. The decrease in intragranular acidity wou ld appear to inhibit intracellular Ca2+ release perhaps due to a reduc tion in the free intragranular Ca2+ concentration.