SHORT-TERM CHANGES IN THE CA2-EXOCYTOSIS RELATIONSHIP DURING REPETITIVE PULSE PROTOCOLS IN BOVINE ADRENAL CHROMAFFIN CELLS()

Stimulus-secretion coupling was monitored with capacitance detection i n bovine chromaffin cells recorded in perforated patch mode and stimul ated with trains of depolarizing pulses. A subset of stimulus trains e voked a response with a Ca2+-exocytosis relationship identical to that obtained for single depolarizing pulses (Engisch and Nowycky, 1996). Other trains evoked responses with enhanced or diminished Ca2+ efficac y relative to this input-output function. The probability of obtaining a particular Ca2+-exocytosis relationship was correlated with the amo unt of Ca2+ entry per pulse, such that shorter pulses or smaller curre nts were associated with the greatest efficacy, and longer pulses and larger currents with the lowest efficacy. Apparent enhancements in Ca2 + efficacy were not caused by residual Ca2+ summing between pulses, be cause decreasing the interval between pulses usually reduced efficacy in the same cell; conversely, increasing the interval between pulses d id not prevent an enhanced Ca2+-exocytosis relationship. Apparent decr eases in Ca2+ efficacy were not caused by depletion of an available po ol of release-ready vesicles, because an equivalent amount of total Ca 2+ entry during a single long depolarizing pulse usually evoked a much larger secretory response in the same cell. Finally, there were no st riking differences in global Ca2+ levels monitored with the fluorescen t indicator Fura Red that could account for apparent changes in Ca2+ e fficacy during repetitive stimulus protocols. It appears that in chrom affin cells, the Ca2+-exocytosis relationship is subject to activity-d ependent changes during a stimulus train and can be modulated up or do wn from a basal state accessed by single pulse stimulations.