Acetylcholine- and caffeine-evoked repetitive transient Ca(2+)-activated K+ and C1- 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, Ca(2+)-dependent K+ current and a single transient inward Ca(2+)-dependent C1-current. 3. Nanomolar ACh induced a series of transients in both the K+ and C1- currents; C1- 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 C1- current transients were also induced by 1 mM-caffeine, consistent with caffeine-induced Ca2+ release from the Ca(2+)-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 microM-IBMX and 10 microM membrane-permeable cyclic AMP. Therefore, it seems likely that caffeine is able to inhibit agonist-induced calcium mobilization via a cyclic AMP-dependent pathway.
Smith
P M
PM
Department of Physiology, University of Liverpool.
Gallacher
D V
DV
D000109:Acetylcholine / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002110:Caffeine / Q000378:metabolism / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects*; D018118:Chloride Channels; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008565:Membrane Proteins / Q000187:drug effects*; D051379:Mice; D015221:Potassium Channels / Q000187:drug effects*; D013363:Submandibular Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D015220:Calcium Channels; D018118:Chloride Channels; D008565:Membrane Proteins; D015221:Potassium Channels; D002110:Caffeine; D000242:Cyclic AMP; D000109:Acetylcholine