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.
Department of Pharmacology, Bruno Ceccarelli Center of Peripheral Neuropathies, S. Raffaele Institute, University of Milano, Italy.
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P
D'Andrea
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D
Zacchetti
J
J
Meldolesi
F
F
Grohovaz
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