AJP - Gastrointestinal and Liver Physiology, Vol 242, Issue 5 513-G521, Copyright © 1982 by American Physiological Society
Stimulation of pancreatic acinar secretion: increases in cytosolic calcium and sodium
J. O'Doherty and R. J. Stark
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+.
