Calcium and pH homeostasis in neurons during hypoxia and ischemia

One of the important events during hypoxia or ischemia in the brain (or other organs for that matter, including the myocardium) is the accumulation of Ca2+ ions intracellularly. Although various studies have shown various sources of and routes for Ca2+ entry and accumulation, it is clear now that it is likely that there is a multitude rather than a single mechanism for this accumulation. In this review, we highlight this Ca2+ accumulation during low O2 states and discuss some of the mechanisms leading to accumulation for two main reasons: (a) an accumulation of Ca2+ in the cytosol has been proven to be deleterious for cell function although this accumulation of Ca2+ and consequences represent only a limited view of events that can lead to cell injury during such stress and (b) developing therapeutic strategies involving the reduction or elimination of this accumulation depends, by and large, on the mechanism of entry. In addition to reviewing some of these Ca2+ events, we will also review the relation between pH (H+) and Ca2+ since these two ions and their regulation are tied to each other in a major way. For example, extracellular acidosis, which can occur during ischemia, has a remarkable effect on the function of some of the Ca2+ entry routes.