The retina of the eye contains photoreceptors, and in many organisms the sensitivity of the retina to light can change. The horseshoe crab, Limulus, is an animal that has been used for many years as a model for vision because it has particularly large compound eyes, with large cells that are relatively accessible for physiological and biochemical studies. In Limulus, retinal sensitivity is regulated by two factors, light itself, which decreases the sensitivity, and nerves coming from the brain to the eye, called efferent innervation, which increase the sensitivity of the eye to light. This project addresses the largely unknown biochemical mechanisms initiated by light and by efferent innervation in Limulus photoreceptors, and explores their interactions at the intracellular level. In particular, changes produced in intracellular calcium ion concentration profoundly influence photoreceptor sensitivity. Internal calcium may exert its effects by calcium regulation of enzyme processes, such as protein kinase activity and protein phosphorylation. Biochemical tools are used to isolate and characterize one of the interesting calcium-activated kinases (known as CaCAM-PK) that also may remain active even in the absence of further calcium elevation. This property means this kinase can be a kind of molecular activating switch. Another protein kinase studied depends on calcium and phospholipid, and acts on photoreceptor proteins. These studies will contribute significantly to our knowledge of how the sensitivity of photoreceptors is regulated, and also how calcium influences the function of cells in general.