Mechanism of [Ca2+]i oscillations in rat chromaffin cells. Complex Ca(2+)-dependent regulation of a ryanodine-insensitive oscillator.
In the population of primary cultured rat chromaffin cells, over half exhibited spontaneous [Ca2+]i oscillations, whereas most others were induced to oscillate by low concentrations of bradykinin or KCl. [Ca2+]i spots were observed to pulsate in a defined cytoplasmic area (the oscillator). In silent cells those spots remained discrete, whereas in oscillating cells the [Ca2+]i increase expanded to occupy the entire cytoplasm. Alternation of these discrete and expanded events was observed 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 reticulum Ca(2+)-ATPase-type Ca2+ pump(s) to be crucial for the functioning of the oscillator. Effects of other treatments were variable, depending on the concomitant [Ca2+]i changes. Oscillations were blocked when EGTA or nitrendipine decreased Ca2+ influx and thus [Ca2+]i; they were also blocked when [Ca2+]i was markedly increased by excess KCl, bradykinin, or ryanodine. When in contrast the [Ca2+]i increases induced by the latter agents remained moderate, oscillations were stimulated. The rhythmic activity of rat chromaffin cells appears, therefore, to operate under a complex regulation that requires [Ca2+]i within an appropriate operative range and does not involve directly the ryanodine receptor but might rely on the activation of IP3 receptors.
D'Andrea
P
P
Department of Pharmacology, Bruno Ceccarelli Center of Peripheral Neuropathies, S. Raffaele Institute, University of Milano, Italy.
Zacchetti
D
D
Meldolesi
J
J
Grohovaz
F
F
D000311:Adrenal Glands / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects; D000252:Calcium-Transporting ATPases / Q000187:drug effects; D002837:Chromaffin Granules / Q000187:drug effects / Q000378:metabolism*; D004533:Egtazic Acid / Q000494:pharmacology; D005260:Female; D051381:Rats; D017207:Rats, Sprague-Dawley; D012433:Ryanodine / Q000494:pharmacology*
D015220:Calcium Channels; D012433:Ryanodine; D002110:Caffeine; D004533:Egtazic Acid; D000252:Calcium-Transporting ATPases; D002118:Calcium