Cell Calcium Extrusion Systems and their Role in Epileptogenesis

ABSTRACT

The precise control for maintenance of a normal intracellular calcium concentration in eukaryote cells is accomplished by several systems located at the plasma membrane, as well as several internal membrane systems. Neurons are especially sensitive to changes in these control systems, since when fail and calcium homeostasis disturbed, the cell's metabolism is immediately modified and a pathological condition emerges. Such a condition has been associated with epileptogenesis, and especially to those mechanisms associated to calcium entrance or ON mechanisms. On the other hand, calcium extrusion mechanisms or OFF mechanisms, have been investigated to a lesser extent and therefore remain much less understood. Here, we present a review of these calcium extrusion systems located at the plasma membrane considered to be critical in the process of epileptogenesis; first of all the plasma membrane calcium ATPase (PMCA) as the catalytic moiety of the enzyme that moves calcium outwards in an energy-dependent fashion, and the Na⁺/Ca²⁺ exchanger (NCX) coupled to the (Na⁺/K⁺)-ATPase. Based on present knowledge considering the wide range of isoforms found for PMCA and NCX and their specific kinetic characteristics, a hypothesis for their participation on the OFF mechanisms related to the genesis of epilepsy is discussed.