Turnabout in vision: messenger unmasked.

A small molecule called cyclic GMP has now been recognized by scientists as the crucial messenger chemical in both types of cells that sense light in animals' eyes. Light striking the retina of the eye trigges in these photoreceptor cells a cascade of molecular events that eventually generates the electricla signals essential for vision. For almost 15 years, scientists had favored a hypothetical description of this cascade in which light released calcium from storage within a photoreceptor cell, and this "messenger" calcium interacted with channels in the outer membrane to produce the electrical signal.

The recent direct evidence that the internal messenger is cyclic GMP rather than calcium ions comes out of experiments with a powerful, relatively new technique called "patch clamping" (SN: 11/7/81, p. 295). Rather than dealing with all the complexities of a cell, the patchclamp technique isolates a small circular segment of outer membrane from a photoreceptor cell--a rod or a cone. Solutions containing calcium ions or cyclic GMP are applied to each side of this membrane patch, and channel activity is monitored.

Such experiments demonstrate that exposing the inner surface of the rod cell the channels to open, but calcium does not have this effect. These results were reported earlier this year by several independent research teams led by Evgeniy E. Fesenko at the USSR Academy of Sciences in Pushchino, King-Wai Yu at the University of Texas Medical Branch in Galveston, T.D. Lamb at the University of Cambridge in England, and W.H. Cobbs and E.N. Pugh Jr. at the University of Pennsylvania in Philadelphia.

Cones have always been more difficult than rods to use in experiments, and so have remained more mysterious. The geometry of a rod cell demands that there be some messenger substance; the light-sensing molecules, rhodopsins, sit in membrane disks that are not continuous with the outer membrane containing the ion channels responsible for the electrical signal. But in cones, the light-sensing molecules are located on deep infoldings of the outer membrane--so a messenger chemical might not be required.

In the Sept. 5 NATURE, however, two research groups--those of Yau and of Cobbs and Pugh -- report that cones of catfish and of larval tiger salamander do use cyclic GMP as a messenger. This finding was somewhat unexpected because biochemical experiments had suggested that light modulates the level not of cyclic GMP but of the related molecule, cyclic AMP.

In both rods and cones the action of cyclic GMP is a biochemical novelty. Scientists had previously observed that in other cells, cyclic GMP mediates the activity of membrane channels via an enzyme reaction, called phosphorylation. But in the photoreceptor cells the cyclic GMP acts directly on the channels, allowing a faster response time. Now the scientists are asking whether the same mechanism exists in other cells.