Plasma membrane mechanisms for intracellular calcium regulation in squid axons

The long term regulation of the cytosolic ionized Ca is the consequence of two separate Ca transport mechanisms present in most eucaryotic cells: a high-affinity and low-capacity system which is in charge of extruding Ca during resting conditions (the Ca pump) and a low affinity and high-capacity system (Na/Ca exchange) designed not only to extrude Ca2+ ions when the Cai raises above certain levels, but also to led Ca into the cell under conditions that favor the reverse reaction of the exchange, such as increase in Nai, decrease in external Na and membrane depolarization. Experiments in dialyzed and voltage clamped squid axons show that the Na/Ca exchange system is a complex mechanism in which several ligands normally present in the cytosol interact with the carrier. This should be taken into account when measuring kinetic properties of the Na/Ca exchange. Of great interest is the fact that Na/Ca exchange is subject of enzymatic regulation (phosphorylation/dephosphorylation), which in turn is regulated by the levels of Cai2+. More evidence is needed from both isolated membrane preparations and in vivo systems to answer several questions including the characterization of the partial reactions of the exchange system, the factors that modulate the affinity of the transport sites for Na and Ca, the stoichiometry (constant or variable?), the current generated by the exchanger and finally, the biochemical structure of the antiporter.