[Ca2+]i oscillations in rat chromaffin cells: frequency and amplitude modulation by Ca2+ and InsP3

Rat chromaffin cells in primary culture exhibit oscillations of cytosolic Ca2+ concentration, sustained by the rhythmic discharge of Ca2+ from specialized intracellular stores. Each Ca2+ spike starts from a discrete region of the cell (pacemaker), and then propagates across the entire cytosol. Spike initiation and propagation, governing the oscillation frequency and amplitude respectively, appeared to be controlled by different mechanisms. The pacemaker was found to be directly activated by increases of cytosolic Ca2+ concentration obtained by either K+ depolarization or nicotinic stimulation. On the other hand, muscarinic or B2 stimulation was required for an efficient spreading to occur, thus suggesting a key role of InsP3 in the signal propagation. The pacemaker displayed an autonomous activity, as documented by the presence of local Ca2+ discharges, which were not necessarily accompanied by spreading to the rest of the cell. This uncoupling could be stimulated by the selective increase of the pacemaker firing rate, due to the rise of the intracellular Ca2+ concentration. Modulation of Ca2+ spike amplitude by treatments affecting either the pacemaker or the spreading phase might be related to quantal Ca2+ release from functionally discrete stores.