The role of cell calcium in current approaches to toxicology.

All cells contain elaborate systems for the spatial and temporal regulation of the calcium ion, [Ca2+]i, and diverse Ca2+ receptor and biochemical response systems that are regulated by these changes in [Ca2+]i. Toxicants that perturb the mobilization or homeostasis of [Ca2+]i will place the regulation of these processes outside the normal range of physiological control. Many classes of chemical toxicants, including metals, solvents, and pesticides, may have particular aspects of cell calcium as key cellular and molecular targets of toxicant action. However, experimental proof of these targets as a specific site of toxicant action is challenging and technically difficult as a result of the complexity and diversity of these processes. To fully establish and understand the target role of the calcium messenger system in toxicant action, it is necessary to distinguish between the effects of a toxicant on (a) the calcium mobilization and homeostatic processes, (b) the calcium-mediated processes, and (c) from those processes which co-regulate or counter-regulate these calcium-mediated processes. As our understanding of the calcium messenger system expands, these insights will be increasingly applied to understanding the mechanisms of action of toxic chemicals.