Intracellular effects of aluminium on receptor-activated cytoplasmic Ca2+ signals in pancreatic acinar cells

Abstract

The hypothesis that intracellular aluminium may interfere with cytoplasmic Ca2+ signals evoked by the activation of receptors linked to inositol lipid hydrolysis has been tested. Single mouse pancreatic acinar cells were used, because there is much information in this system on the mechanism by which acetylcholine (ACh) evokes cytoplasmic Ca2+ oscillations (spiking) and these spikes can be monitored in internally perfused cells by measuring the Ca(2+)-dependent chloride current. ACh normally evokes repetitive Ca2+ spikes, but when aluminium (1 microM-1 mM) is present in the internal perfusion solution the responses are reduced or absent. When aluminium is acutely infused into the internal perfusion solution the ACh-evoked Ca2+ signals quickly disappear. Aluminium also inhibits Ca2+ signals evoked by the Ca2+ releasing agent caffeine. Preliminary results suggest that silicic acid may protect against the toxic effects of aluminium. Silicic acid and citrate, in the absence of added Al3+, have the effect of enhancing the ACh-evoked Ca2+ signals. This could be due to binding of traces of Al3+ in the solutions. We conclude that aluminium can disrupt receptor-activated cytosolic Ca2+ signals when present inside cells.