Implicating the role of plasma membrane localized calcium channels and exchangers in stress-induced deleterious effects

Stress-induced increase in intracellular calcium (Ca(2+)) has been demonstrated to produce various deleterious effects in the body. The rise in intracellular Ca(2+) (particularly neuronal) in response to stress has been mainly attributed to opening of voltage gated L-type Ca(2+) channels. The role of P/Q-, N-, R- and T-type Ca(2+)channels, and plasma membrane localized exchangers such as Na(+)/Ca(2+) exchanger and Ca(2+) ATPase has also been implicated in increasing intracellular Ca(2+) in response to stress. Stress-induced changes in Ca(2+) currents has been mainly attributed to increased release of corticosterone (activation of glucocorticoid receptors in the hippocampus) and catecholamine release as a consequence of activation of Hypothalamic-Pituitary-Adrenal (HPA) axis and sympathetic neural system, respectively. Stress-induced increase intracellular Ca(2+) may trigger various deleterious signaling pathway including free radical generation, apoptosis, increased synaptic release of glutamate and synthesis/release of cytotoxic cytokines that may be responsible for damaging effects associated with stress. The present review discusses the mechanisms involved in stress-induced rise in intracellular Ca(2+) levels and subsequent implications of increased Ca(2+) levels in stress.