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Preparation of Pancreatic Acinar Cells for the Purpose of Calcium Imaging, Cell Injury Measurements, and Adenoviral Infection
Published on: July 5, 2013
Cyclic AMP accelerates calcium waves in pancreatic acinar cells
Ahsan U Shah1, Wayne M Grant, Sahibzada U Latif
1Dept. of Pediatrics, Yale University School of Medicine, 333 Cedar St., FMP408, PO Box 208064, New Haven, CT 06520, USA.
Summary
Cyclic AMP (cAMP) accelerates calcium (Ca2+) waves in pancreatic acinar cells by affecting ryanodine receptors. This modulation involves both protein kinase A (PKA) and Epac pathways, impacting cellular signaling.
Area of Science:
- Cell Biology
- Physiology
- Biochemistry
Background:
- Cytosolic calcium (Ca2+) flux is critical for pancreatic acinar cell function and pathology.
- The role of cyclic AMP (cAMP) in modulating Ca2+ signaling dynamics, specifically apical-to-basal waves, remains incompletely understood.
Purpose of the Study:
- To investigate how cAMP influences the speed and characteristics of Ca2+ waves in rat pancreatic acinar cells.
- To determine the involvement of cAMP-dependent protein kinase (PKA) and exchange protein directly activated by cAMP (Epac) in mediating these effects.
Main Methods:
- Isolated rat pancreatic acinar cells were stimulated with carbachol.
- Vasoactive intestinal polypeptide (VIP) or 8-bromo-cAMP (8-Br-cAMP) were used to modulate cAMP levels.
- Confocal laser-scanning microscopy monitored intracellular Ca2+ (Ca2+) dynamics.
- Inhibitors of ryanodine receptors (dantrolene) and PKA (PKI) were employed.
Main Results:
- cAMP significantly increased the speed of apical-to-basal Ca2+ waves induced by carbachol.
- The Ca2+ rise time was reduced by cAMP, particularly in the basal region.
- The enhancement of wave speed by cAMP was attenuated by ryanodine receptor and PKA inhibition.
- Specific Epac activation mimicked the effects of VIP and 8-Br-cAMP on wave speed.
Conclusions:
- cAMP accelerates the propagation speed of Ca2+ waves in pancreatic acinar cells.
- This acceleration is likely mediated by modulation of ryanodine receptors (RyRs).
- Both PKA and Epac pathways independently contribute to the cAMP-mediated enhancement of Ca2+ wave speed.
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