Rundown of secretion after depletion of intracellular calcium stores in bovine adrenal chromaffin cells

In this study, the relationship between intracellular calcium stores and de polarization-evoked stimulation was examined in bovine chromaffin cells, us ing changes in membrane capacitance to monitor both exocytosis and endocyto sis. Cells were voltage-clamped using the perforated whole-cell patch confi guration to minimize alterations in intracellular constituents. Control cel ls exhibited reproducible secretory responses each time the cell was stimul ated. However, the same stimulation protocol elicited progressively smaller secretory responses in cells where their intracellular calcium store was e mptied by thapsigargin. Transient elevation of the intracellular calcium co ncentration with a brief histamine treatment enhanced subsequent secretory responses in control but not in thapsigargin-treated cells. A series of dep olarizations to -20 mV, which allowed small amounts of Ca2+ influx but whic h by itself did not trigger catecholamine secretion, enhanced subsequent ex ocytosis in both control and thapsigargin-treated cells. Caffeine-pretreate d cells exhibited a rundown in the secretory response that was similar to t hat produced by thapsigargin. These results suggest that brief elevations o f [Ca2+](i) could enhance subsequent secretory responses, In addition, the data suggest that intracellular calcium stores are vital for the maintenanc e of exocytosis during repetitive stimulation.