Cytosolic calcium concentrations and cell death in vitro

Although the concept of Ca2+ ions as mediators of cytotoxicity has been accepted, there have been past difficulties in correlating intra-cellular Ca2+ levels and neurotoxicity. It is now apparent that neurons that succumb to Ca2+ loading sustain a failure of Ca2+ homeostatic mechanisms due to processes set into motion very early following the initial insult. Recent work suggests that there exists a linear correlation between total neuronal Ca2+ loading and neurodegeneration. However, the slope of this linear relationship may be modulated by numerous factors such as the transmembrane Ca2+ gradient, the route of Ca2+ influx, and the presence of various Ca2+ buffering and extrusion systems within the cell. In the future, processes responsible for neurodegeneration may be better understood through the study of the subcellular interplay between membrane receptors, second messenger systems, and Ca2+ buffering mechanisms. Refinements on past techniques will be necessary to place further quantitative boundaries on global and subcellular neurotoxic Ca2+ increases.