[CA2- FREQUENCY AND AMPLITUDE-MODULATION BY CA2+ AND INSP(3)(]I OSCILLATIONS IN RAT CHROMAFFIN CELLS )

Rat chromaffin cells in primary culture exhibit oscillations of cytoso lic Ca2+ concentration, sustained by the rhythmic discharge of Ca2+ fr om specialized intracellular stores. Each Ca2+ spike starts from a dis crete region of the cell (pacemaker), and then propagates across the e ntire cytosol, Spike initiation and propagation, governing the oscilla tion frequency and amplitude respectively, appeared to be controlled b y different mechanisms. The pacemaker was found to be directly activat ed by increases of cytosolic Ca2+ concentration obtained by either Kdepolarization or nicotinic stimulation. On the other hand, muscarinic or B-2 stimulation was required for an efficient spreading to occur, thus suggesting a key role of InsP(3) in the signal propagation. The p acemaker displayed an autonomous activity, as documented by the presen ce of local Ca2+ discharges, which were not necessarily accompanied by spreading to the rest of the cell, This uncoupling could be stimulate d by the selective increase of the pacemaker firing rate, due to the r ise of the intracellular Ca2+ concentration. Modulation of Ca2+ spike amplitude by treatments affecting either the pacemaker or the spreadin g phase might be related to quantal Ca2+ release from functionally dis crete stores.