Calcium homeostasis in vertebrate retinal rod outer segments

The outer segments of vertebrate retinal rod photoreceptors (ROS) exhibit dynamic Ca2+ fluxes. In darkness, Ca2+ continuously enters via the light-sensitive, cGMP-gated channels and this requires the presence of a powerful Ca2+ extrusion mechanism in the ROS plasma membrane. Our laboratory has characterized a Na/Ca+K exchanger in the ROS plasma membrane, which utilizes both inward Na+ gradient and outward K+ gradient to extrude Ca2+. Here, I review our work on the functional properties of the Na/Ca+K exchanger including the stoichiometry, ion binding sites and regulation of Ca2+ transport via Na/Ca+K exchange. Inactivation of the Ca2+ extrusion mode of the Na/Ca+K exchanger will be discussed as a mechanism to prevent lowering of cytosolic free Ca2+ to undesirably low values of < 1 nM that are expected from the coupling stoichiometry of the Na/Ca+K exchanger and that are expected to occur when Ca2+ influx via the cGMP-gated channels is interrupted during saturation of rod photoreceptors in bright light. This review also reexamines the contribution of internal Ca2+ stores (i.e. disks) to Ca2+ homeostasis in ROS.