Photoreceptor Biology

Edited by Karen Young Kreeger M.P. Gray-Keller, P.B. Detwiler, "The calcium feedback signal in the phototransduction cascade of vertebrate rods," Neuron, 13:849-61, 1994. (Cited in more than 30 publications through June 1996) Comments by Mark Gray-Keller, University of Washington, Seattle The biochemical reactions governing vision are some of the most complex and sensitively regulated processes in the human body. In vertebrate retinal photoreceptors-called the rods and cones-calcium ions play a key role in the process that converts light into an electrical signal. This transformation of a physical stimulus into a biologically useful signal is the first step in vision. EYE-OPENER: University of Washington's Mark Gray-Keller and colleagues studied the role of calcium feedback signals in science. "I think this paper has received a lot of attention because we describe for the first time the magnitude and time course of the change in intracellular calcium that accompanies the light response in isolated rod photoreceptor cells," says Mark Gray-Keller, a postdoctoral fellow in the laboratory of Peter Detwiler, a professor in the department of physiology and biophysics at the University of Washington. "Calcium serves a critical function in the biochemistry of vision," explains Gray-Keller. "It acts as a feedback messenger that regulates a number of enzymes in the phototransduction cascade, [which] couples the absorption of light by the visual pigment rhodopsin to the closure of ion channels in the rod-cell-surface membrane. The closure of the ion channels generates an electrical signal, which leads to a fall in intracellular calcium. The decrease in calcium coordinates the termination of the transduction cascade and orchestrates the recovery process that returns the rod to its resting dark state." The first part of the paper describes the procedures that Gray-Keller and Detwiler developed to track the light-induced decrease in intracellular calcium. They compared two calcium-sensitive fluorescent dyes-free Indo and Indo-dextran-and discovered that only Indo-dextran provided a reliable measure of internal calcium levels. Gray-Keller reaches back to the earlier development of the field of photoreceptor biology to explain why the paper is so highly cited: "There are labs all over the world that have been studying the biochemistry of phototransduction, mostly by isolating the individual enzymes in the pathway. The attention of the field has focused greatly on the potential feed-back role that calcium plays in transduction. We have known that light results in a fall in internal calcium and that key reactions in the phototransduction cascade are sensitive to the change in calcium." By devising methods to monitor the decrease in intracellular calcium, Gray-Keller and Detwiler have been able to investigate the physiological changes in calcium that occur under various conditions. He also points out that "vertebrate phototransduction is the prototypic and most thoroughly understood example of a G-protein-coupled signal transduction process. As a result, the work we have done on calcium measurements in rods has broad relevance to the general problem of cellular signaling." In the future, their basic model may also have therapeutic applications. "Calcium is one of these 'magic bullet' ions," notes Gray-Keller. "It seems to be involved in almost every biochemical process. There are a variety of visual diseases in photoreceptors that are thought to be at least related to changes in internal calcium. "We have a paper that will appear in the August issue of Neuron [M.P. Gray-Keller, P.B. Detwiler, Neuron, Vol.17 #2 p.323-331, August 1996] that extends the work described in our 1994 Neuron paper," he adds. "We've taken advantage of what we learned two years ago to investigate the relationship between calcium and the adaptational changes in the transduction cascade that occur when photoreceptors are exposed to steady light. These experiments address some basic questions about calcium and the molecular mechanisms that underlie the adaptational changes in this classical example of a G-protein-coupled signaling pathway."

Photoreceptor Biology

The Scientist Staff

Interested in reading more?

Become a Member of