Interactions between inositol trisphosphate and Ca2+ dependent Ca2+ release mechanisms on the endoplasmic reticulum of permeabilised bovine aortic endothelial cells.

In this paper we describe data from cultured bovine aortic endothelial (BAE) cells demonstrating a Ca2+ induced Ca2+ release (CICR) process which appears to have pharmacological properties different from CICR mechanisms in other cell types. CICR was measured in saponin permeabilised cells in which the internal stores had been preloaded with 45Ca2+. Step increases in the free Ca2+ concentration of the bathing solution, from 10 nM up to 10 microM were found to increase 45Ca2+ loss. This process was completely inhibited by ruthenium red. Caffeine induced a small release of 45Ca2+ and the response to a subsequent stimulation with a Ca2+ step was reduced. In intact cells, ryanodine activated small oscillations in intracellular Ca2+ in the presence, but not the absence, of external Ca2+. However, in permeabilised cells, ryanodine had no effect on either basal efflux or the increased efflux of 45Ca2+ seen following a step increase in free Ca2+. These data suggest the operation of a ruthenium red sensitive but ryanodine insensitive CICR mechanism on the endoplasmic reticulum (ER) which may also be modulated by caffeine. An IP3 dependent 45Ca2+ release was also observed. In the presence of ruthenium red, the IP3 induced 45Ca2+ release was reduced suggesting that CICR may operate to amplify the magnitude of the IP3 response. The Ca2+ dependence of the IP3 induced release was also measured. Co-operativity between IP3 and Ca2+ could not be detected between 100-300 nM Ca2+. The results suggest that the regulation of IP3 induced Ca2+ release may be different in BAE cells, and point to the operation of a 'novel' CICR process and to complex interactions between Ca2+ release systems in BAE cells.