ACETYLCHOLINE-EVOKED AND CAFFEINE-EVOKED REPETITIVE TRANSIENT CA2+-ACTIVATED K+ AND CL- CURRENTS IN MOUSE SUBMANDIBULAR CELLS

1. Resting and acetylcholine-induced membrane currents were measured in single mouse submandibular acinar cells using the patch-clamp whole-cell current recording technique. 2. Micromolar ACh activated a large, sustained outward, Ca2+-dependent K+ current and a single transient inward Ca2+-dependent Cl-current. 3. Nanomolar ACh induced a series of transients in both the K+ and Cl-currents; Cl- current activation was now observed throughout the period of agonist application. We consider this repetitive transient current activation better able to support sustained fluid and electrolyte secretion than the response elicited by a high dose of agonist. 4. Repetitive K+ and Cl- current transients were also induced by 1 mM-caffeine, consistent with caffeine-induced Ca2+ release from the Ca2+-sensitive Ca2+ stores which are thought to comprise part of the pathway for activation of secretion. 5. The ACh-induced current transients were inhibited by 10 mM-caffeine, 100-mu-M-IBMX and 10-mu-M membrane-permeable cyclic AMP. Therefore, it seems likely that caffeine is able to inhibit agonist-induced calcium mobilization via a cyclic AMP-dependent pathway.