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Science 4 January 1991:
Vol. 251. no. 4989, pp. 75 - 78
DOI: 10.1126/science.1986413
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Articles

Science, Vol 251, Issue 4989, 75-78
Copyright © 1991 by American Association for the Advancement of Science

articles

Generation of calcium oscillations in fibroblasts by positive feedback between calcium and IP3

AT Harootunian, JP Kao, S Paranjape, and RY Tsien

Howard Hughes Medical Institute M-047, University of California San Diego, La Jolla 92093-0647.

A wide variety of nonexcitable cells generate repetitive transient increases in cytosolic calcium ion concentration ([Ca2+]i) when stimulated with agonists that engage the phosphoinositide signalling pathway. Current theories regarding the mechanisms of oscillation disagree on whether Ca2+ inhibits or stimulates its own release from internal stores and whether inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DG) also undergo oscillations linked to the Ca2+ spikes. In this study, Ca2+ was found to stimulate its own release in REF52 fibroblasts primed by mitogens plus depolarization. However, unlike Ca2+ release in muscle and nerve cells, this amplification was insensitive to caffeine or ryanodine and required hormone receptor occupancy and functional IP3 receptors. Oscillations in [Ca2+]i were accompanied by oscillations in IP3 concentration but did not require functional protein kinase C. Therefore, the dominant feedback mechanism in this cell type appears to be Ca2+ stimulation of phospholipase C once this enzyme has been activated by hormone receptors.


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