Generation of calcium oscillations in fibroblasts by positive feedback between calcium and IP3 |
| |
| Authors: | A T Harootunian J P Kao S Paranjape R Y Tsien |
| |
| Institution: | Howard Hughes Medical Institute M-047, University of California San Diego, La Jolla 92093-0647. |
| |
| Abstract: | 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. |
| |
| Keywords: | |
|
|
