ALBUMIN STIMULATES UPTAKE OF CALCIUM INTO SUBCELLULAR STORES IN RAT CORTICAL ASTROCYTES

1. When albumin from either plasma or serum is applied at low concentr ations to cortical astrocytes a decrease in the level of [Ca2+], is ob served. At higher concentrations trains of calcium spices are seen. 2. Removal of the polar lipids which are normally bound to native albumi n abolishes the ability to induce spikes, but the decrease in [Ca2+](i ) is unaffected. The decrease is abolished by the denaturation of albu min and is not reproduced by a number of other proteins, and is theref ore a specific action of albumin. We conclude that native albumin has a dual agonist action: the decrease in [Ca2+](i) is induced by the alb umin protein molecule, while the spikes are induced by a lipid normall y bound to it. 3. The decrease is rapid (fastest tau = 12 s) and the r ate is dependent on the concentration of albumin. [Ca2+](i) falls from 77 nM to around 34 nM in the presence of saturating levels of albumin , and this level appears to be maintained indefinitely. 4. The decreas e is due to an uptake of calcium into subcellular stores, as it is not abolished by removal of external Ca2+ or Na+ but is abolished by thap sigargin and cyclopiazonic acid, which are specific inhibitors of the endoplasmic reticulum Ca2+-ATPase. 5. When the state of store filling after albumin application is probed with a pulse of glutamate it can b e seen that stores hh with the same time course as the decrease in [Ca 2+](i). The low level of [Ca2+](i) in albumin must therefore be mainta ined by a suppression of calcium influx rather than by a continued upt ake into stores. 6. The calcium uptake potentiates the efficacy of low concentrations of calcium-releasing agonists such as glutamate and br adykinin by almost an order of magnitude. 7. A possible function for t he calcium uptake caused by albumin is to potentiate the production of calcium spike trains by promoting refilling of calcium stores in the intervals between spikes. The uptake may play a role in the response o f astrocytes to damage in the CNS.