Intercellular calcium waves in rat pancreatic acini: mechanism of
transmission.
Yule, David I., Edward Stuenkel, and John A. Williams.
Department of Physiology, University of Michigan Medical School,
University of Michigan, Ann Arbor, MI-48105
APStracts 3:0131C, 1996.
Digital-imaging microfluorimetry together with microinjection of
marker/messenger molecules was utilized to investigate intercellular
calcium signaling in rat pancreatic acinar cells. Stimulation of
acini with low concentrations of secretagogues (CCK <100 pM; CCh
< 1 [mu]M) resulted in the appearance of asynchronous but
coordinated increases in Ca2+ which appeared to pass in a `wave like'
fashion between cells. In contrast, at higher supermaximal
concentrations of agonists (CCK > 300 pM; CCh > 1 [mu]M)
which induce a large `peak and plateau' intracellular Ca2+ signal,
all cells in the acinus appeared to increase [Ca2+] in synchrony.
Microinjection of lissarhodamine, a marker of gap-junctional
permeability, to cells previously loaded with fura-2, allowed the
simultaneous measurement of gap-junctional coupling and [Ca2+].
Stimulation with supermaximal concentrations of agonists resulted in
the attenuation of junctional permeability, while during stimulation
with physiologic concentrations of agonist junctional communication
remained operable. Injection of 1,4,5-IP3 into one cell of an acinar
cluster resulted in the generation of a Ca2+ signal in the injected
cell and adjacent cells. In contrast, injection of CaCl2 itself did
not result in propagation of the signal. When CaCl2 was injected into
cells which had been previously stimulated with a threshold
concentration of CCK, propagation of a signal was observed between
cells. On the basis of these data a model is proposed in which Ca2+
acts as co-agonist with 1,4,5-IP3 to potentiate the Ca2+ releasing
action of 1,4,5-IP3 and by diffusion of the two molecules through
gap-junctions underlies intercellular signaling in acinar cells. Gap
-junctional communication may be an important factor in amplifying a
threshold signal produced in one cell throughout the acinus resulting
in enhanced stimulated secretion in acinar preparations as compared
to preparations of isolated cells.
Received 10 January 1996; accepted in final form 12 April 1996.
APS Manuscript Number C10-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 1 May 96