EXTRACELLULAR CALCIUM HAS DISTINCT EFFECTS ON FAST AND SLOW COMPONENTS OF THE DEPOLARIZATION-INDUCED SECRETORY RESPONSE FROM CHROMAFFIN CELLS

An increase in extracellular Ca2+ concentration from 0.25 to 10 mM enh anced secretion of norepinephrine and epinephrine induced by a high ex tracellular K+ concentration (75 mM). The increment in extracellular C a2+ concentration also increased the observed peak inward Ca2+ current in response to long (10-s) depolarizing pulses from a holding potenti al of -55 mV to +5 mV, from about -26 to -400 pA. However, the total a mount of Ca2+ influx into the cell only increased when the extracellul ar Ca2+ concentration was raised from 0.25 to 1 mM and then remained c onstant up to 10 mM extracellular Ca2+. ATP is cosecreted with catecho lamines following a depolarizing stimulus. Kinetic studies indicated t hat ATP secretion had two components with time constants, in the prese nce of 2.5 mM extracellular Ca2+, of similar to 4 and 41 s, being the fast component of secretion produced by the exocytosis of similar to 2 20 chromaffin granules. The results suggest that, for a given depolari zing stimulus, the size and rate of release for the fast and slow comp onents of secretion are dependent on extracellular Ca2+ concentration.