The pattern of agonist-evoked cytosolic Ca2+ oscillations depends on the resting intracellular Ca2+ concentration

Abstract

The agonists acetylcholine (ACh) and cholecystokinin (CCK) have been shown to evoke markedly different patterns of cytosolic Ca2+ oscillations in the same isolated pancreatic acinar cells. ACh induces high frequency sinusoidal oscillations (spiking) associated with activation of Ca2+ influx. CCK evokes longer lasting discrete transients separated by long intervals, and these low frequency transients persist for many minutes in the absence of extracellular Ca2+. Using digital imaging of fura-2 fluorescence, we have now monitored the free cytoplasmic Ca2+ concentration ([Ca2+]i) simultaneously in many individual cells from the same population. In the resting condition [Ca2+]i ranged from about 50 to 300 nM. When the resting [Ca2+]i was below 150 nM, ACh (50-100 nM) invariably evoked typical high frequency spiking. In the majority of cells which had a resting [Ca2+]i higher than 150 nM, ACh also evoked low frequency transients. Although initiated by ACh, these transients displayed the temporal and functional characteristics of the CCK-evoked transients. Removal of extracellular Ca2+ for a few minutes had no effect on this type of oscillation, whereas such a procedure reversibly abolished the ACh-evoked high frequency response. For the response evoked by 10-30 pM Ca2+ signal amplitude and the resting [Ca2+]i. Because the Ca2+ signal amplitude and the resting [Ca2+]i. Because CCK could never induce high frequency spiking there is some receptor specificity in dictating the time course of Ca2+ oscillations, but the resting [Ca2+]i is a major determinant of the Ca2+ signal pattern.