Calcium Transport Pathways of Pancreatic Acinar Cells

Abstract

The control of [Ca2+]i in resting and stimulated pancreatic acinar cells is achieved by at least four Ca2+ transporting pathways. Conductive pathways in the plasma and ER membranes allow Ca2+ influx into the cytosol while ATP-fueled Ca2+ pumps remove Ca2+ from the cytosol. The contribution of these Ca2+ pathways to cytosolic Ca2+ is illustrated in the Figure 2. In the resting cells, [Ca2+]i is determined by the rates of Ca2+ influx and efflux across the plasma membrane. Cytosolic Ca2+ is buffered to approximately 150 nM. The rate of Ca2+ pumping across the plasma membrane is equal to the rate of Ca2+ influx, which keeps [Ca2+]i at a constant level. The buffering of cytosolic Ca2+ prevents large fluctuations in [Ca2+]i. The ER contains about 3 nmoles calcium/mg of cell protein. ER calcium is probably also buffered, which results in low free Ca2+ concentration in the ER interior. The Ca2+ permeability of the ER membrane is very low. The low ER free Ca2+ concentration and Ca2+ permeability result in a low rate of Ca2+ pumping by the ER Ca2+ pump. The low pump-leak turnover rate of Ca2+ across the ER membrane minimizes the contribution of the ER to [Ca2+]i in the resting cells. When the cells are stimulated, a sequence of events is initiated, the end result of which is a transient increase in [Ca2+]i. To produce the transient increase in [Ca2+]i, the activity of the four Ca2+ pathways is modified. The sequence of activation of each Ca2+ pathway has not been completely resolved. It is, however, likely that binding of agonist to a receptor is followed by activation of phospholipase C (PLC). PLC catalizes the breakdown of PIP2 to IP3 and diacylglycerol (DAG). In subsequent stimulation periods PIP2 is also hydrolyzed to IcP3. At the onset of stimulation, the properties of the Ca2+ buffer in the ER may be changed so that free Ca2+ concentration in the ER interior is increased. IP3 binds to specific receptors in the ER membrane and activates a Ca2+ conductance. This leads to Ca2+ efflux from the ER to the cytosol and K+ influx from the cytosol to the ER through a K+ conductive pathway. It is unclear if K+ influx is sufficient to balance the charge released as Ca2+. In the case of muscle SR, it was suggested that K+, Mg2+, and H+ influx are required to balance the charge released as Ca2+ (110).(ABSTRACT TRUNCATED AT 250 WORDS)