Stimulation of pancreatic acinar secretion: increases in cytosolic calcium and sodium.
Na+-selective and Ca2+-selective microelectrodes were used to examine the ionic mechanisms regulating acetylcholine (ACh) stimulation of pancreatic secretion. The cytosolic concentrations of free ionized Na+ and Ca2+ ([Na]i, [Ca]i) were determined in unstimulated acinar cells to be 10.5 +/- 0.4 mM and 0.43 +/- 0.03 microM, respectively. By measuring the induced changes in intracellular Ca2+, Na+, and membrane potentials (ECa, ENa, Em), we were able to demonstrate that 5 X 10(-8) M ACh depolarized Em by 4.3 +/- 0.2 mV and increased [Na]i and [ca]i to 12.2 +/- 0.3 mM and 0.58 +/- 0.02 microM, respectively. Stimulation with ACh at concentrations ranging from 10(-8) to 10(-5) M increased [Ca]i from 0.4 microM to between 0.5 and 1.0 microM. Amylase release reached a maximum at 10(-7) M ACh stimulation and progressively decreased at higher concentrations of stimulus. Increasing the stimulus above an optimal concentration appears to reduce or inhibit enzyme release. These experiments provide direct evidence supporting the concept that acinar cell secretion is triggered by increases in [Ca]i and of calcium's ability to act as primary intracellular mediator. Stimulation after removal of extracellular Ca2+ eliminated the increase in [ca]i that is usually observed in secreting cells, while producing the normal depolarization of Em and increase in [Na]i. These studies demonstrate the increases in [Ca]i are derived from an increase in membrane permeability to Ca2+ and the ability of ACh to depolarize the Em by a transmembrane movement of Na+ that is independent of the change in intracellular Ca2+.
D000109:Acetylcholine / Q000494:pharmacology; D000681:Amylases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism*; D005260:Female; D007424:Intracellular Fluid / Q000032:analysis / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D008839:Microelectrodes; D009994:Osmolar Concentration; D010179:Pancreas / Q000033:anatomy & histology / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*
D012964:Sodium; D000681:Amylases; D000109:Acetylcholine; D002118:Calcium