[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.