Regulating transient and sustained changes of cytosolic Ca2+ in rat pancreatic acini

Abstract

The regulation of changes in cytosolic Ca2+ concentration (Cai2+) during exposure to carbachol was studied in rat pancreatic acini loaded with fura-2. With an extracellular Ca2+ concentration (Cao2+) of 2.5 mM, resting Cai2+ is 185 +/- 48 (SD) nM (n = 23), which rises to 696 +/- 222 nM, then falls over 2 min to a stable plateau of 401 +/- 106 nM. With Cao2+ less than 10 nM, carbachol produces an immediate threefold increase in Cai2+ that dissipates over 2-3 min, and Cai2+ steadily falls below prestimulation levels. Atropine prevents all responses to carbachol, and when it is added during a response to carbachol, Cai2+ drops to resting values within seconds. Ca2+ influx is required for the prolonged elevation of Cai2+ during carbachol exposure, but Ca2+ entry is not regulated by an increase in Cai2+ itself nor does Ca2+ enter via voltage-gated L-type channels. The muscarinic receptor-operated Ca2+ entry mechanism is sensitive to Cao2+, since sustained elevations in Cai2+ are maximal at 2.5 mM Cao2+ but are much less pronounced at lower external Ca2+ concentrations.

Sequential activation of different Ca2+ entry pathways upon cholinergic stimulation in mouse pancreatic acinar cells

“…Moreover, a similar finding was attained when PMA or GF109293X was applied during the sustained plateau of CCE (data not shown), showing that PKC can promote Ca¥ influx. Another index of capacitative calcium entry is the plateau phase of the Ca¥ response to calcium-mediated agonists: during Ca¥ mobilization by physiological agonists of pancreatic acinar cells, such as acetylcholine (ACh) and cholecystokinin (CCK), activation of CCE contributes to the maintenance of the Ca¥ signal (Yule & Gallacher, 1988;Hurley & Brinck, 1990). As shown in Fig.…”

Calcium-dependent photodynamic action of di- and tetrasulphonated aluminium phthalocyanine on normal and tumour-derived rat pancreatic exocrine cells

“…Stimulation of AR4-2J ceUls by receptor agonists is known to initiate a transient rise in intracellular calcium. but to sustain this increase some extracellular calcium is also required (Bird et al, 1991) as it is also in normal cells (Hurley & Brinck, 1990 although not the only. explanation for these results is that the target for inhibition of the high basal constitutive secretion by photon activation of the photodynamic agent and the generation of reactive species, especially singlet oxygen, is a calcium-dependent membrane site.…”