1. We have monitored changes in membrane capacitance (ΔC) and conductance (ΔG) induced by muscarinic acetylcholine stimulation in single rat pancreatic acinar cells. 2. Acetylcholine (ACh, 500 nM) induced simultaneous increases of ΔC and ΔG. In contrast, a low concentration (50 nM) of ACh exclusively induced ΔC increases without ΔG. These responses were abolished by the internal perfusion of heparin. This indicates that inositol 1,4,5-trisphosphate-mediated internal Ca2+ mobilization either simultaneously activates exocytosis and ion channels or exclusively initiates exocytosis. In comparison, a low concentration of A23187 selectively activated ion channels but a high concentration activated exocytosis and ion channels simultaneously. 3. These selective response patterns of ΔC and ΔG depend on the choice of agonist and the internal EGTA concentration. From this, we postulated two explanations for the selective action of muscarinic ACh stimulation on exocytosis. First, an area of high [Ca2+](i) spatially close to secretory granules, activates exocytosis. Second, an as yet unknown signalling factor sensitizes the Ca2+ affinity of the exocytotic apparatus.
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