Abstract
Calcium (Ca2+) ions are ubiquitous intracellular messengers governing innumerable functions such as the control of cell growth and differentiation, membrane excitability, exocytosis and synaptic activity. Because of this, neurons must tightly regulate the cytosolic Ca2+ concentration ([Ca2+]i) to achieve a sufficiently high signal-to-noise ratio for efficient Ca- signaling to occur. The resting free [Ca2+]i must remain at very low levels (around 100 nM, or 105 times lower than extracellular [Ca2+]), so that relatively small or localized increases in [Ca2+]i can be used to trigger physiological events such as the activation of an enzyme or an ion channel. Neurons have therefore evolved complex homeostatic mechanisms to control both [Ca2+]i and the intracellular location of Ca2+ ions (for a general review of Ca2+ homeostasis in neurons see refs Blaustein, 1988; Meldolesi et al. 1988; Smith, Augustine, 1988; Miller, 1992). These mechanisms consist of complex interactions between four general categories of events: Ca2+ influx, Ca2+ buffering, internal Ca2+ storage and Ca2+ efflux. Under physiological conditions, a delicate interplay between these processes allows multiple Ca2+ dependent signaling cascades to be regulated independently within the same cell. However, it is widely believed that excessive Ca2+ loading, exceeding the capacity of Ca-regulatory mechanisms, may inappropriately activate Ca-dependent processes which either lie dormant or normally operate at low levels. When over-activated, such processes directly damage neurons or lead to the formation of toxic reaction products which ultimately cause cell death. However, in spite of two decades of research supporting the association between Ca2+ excess and neurotoxicity, the precise molecular mechanisms by which Ca2+ toxicity occurs remain poorly understood.
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Sattler, R., Tymianski, M. (1998). Calcium and Cellular Death. In: Verkhratsky, A., Toescu, E.C. (eds) Integrative Aspects of Calcium Signalling. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-1901-4_13
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