MECHANISM OF [CA2- COMPLEX CA2+-DEPENDENT REGULATION OF A RYANODINE-INSENSITIVE OSCILLATOR(]I OSCILLATIONS IN RAT CHROMAFFIN CELLS )

In the population of primary cultured rat chromaffin cells, over half exhibited spontaneous [Ca2+]i oscillations, whereas most others were i nduced to oscillate by low concentrations of bradykinin or KCl. [Ca2+] i spots were observed to pulsate in a defined cytoplasmic area (the os cillator). In silent cells those spots remained discrete, whereas in o scillating cells the [Ca2+]i increase expanded to occupy the entire cy toplasm. Alternation of these discrete and expanded events was observe d in a few irregularly oscillating cells. Thapsigargin induced prompt blockade of both pulsations and oscillations and prevented recruitment of silent cells to oscillate. This indicates sarcoendoplasmic reticul um Ca2+-ATPase-type Ca2+ pump(s) to be crucial for the functioning of the oscillator. Effects of other treatments were variable, depending o n the concomitant [Ca2+]i changes. Oscillations were blocked when EGTA or nitrendipine decreased Ca2+ influx and thus [Ca2+]i; they were als o blocked when [Ca2+]i was markedly increased by excess KCl, bradykini n, or ryanodine. When in contrast the [Ca2+]i increases induced by the latter agents remained moderate, oscillations were stimulated. The rh ythmic activity of rat chromaffin cells appears, therefore, to operate under a complex regulation that requires [Ca2+]i within an appropriat e operative range and does not involve directly the ryanodine receptor but might rely on the activation of IP3 receptors.