When Mike Varnum, assistant professor, Veterinary and Comparative Anatomy, Pharmacology, and Physiology, visits the aquarium, he looks at the sea creatures a bit differently than the rest of us. What interests him most about a creature is not its bright color or odd shape, but whether it makes a toxin that blocks an ion channel. Oddly, many of the creatures do.
Many toxins, in fact, block specific ion channels, though Varnum uses different agents in his work. Ion channels are pores in the membranes of many different types of cells-highly selective, gated pores-that permit the passage of specific charged particles, or ions, into or out of the cell.
Varnum studies ion channels that are present in the cone cells of the retina of the eye, the cells that allow us to see in the daylight and that give us sharp images and the ability to see in color. These channels allow the passage of both sodium and calcium ions into the cone cell.
What the brain eventually interprets as vision begins when a cone cell, or its counterpart, the rod cell, absorbs a unit of light, or photon. A subsequent cascade of changes within the cell ultimately results in information being passed along a series of nerve cells and, via the optic nerve, into the brain. The cones’ ion channels are the place where the light signal is translated into an electrical signal, a primary means by which the nerve cells transmit information.
One of the more amazing characteristics of cone cells is their ability to respond to light levels that vary in luminance magnitude over a billion-fold range. This is accomplished in part by the cells’ ability to adjust to the wide range of background light levels against which the photons are detected, and ion channels appear to be involved in that process. Varnum and others have determined that the ion channels may help set the sensitivity of the cone cells’ response to photon absorption via their ability to regulate, at least in part, the concentration of calcium within the cell.
When a cone cell absorbs photons, the ion channels close, and the concentration of calcium within the cell is reduced. The lowered concentration ultimately results in increased channel activity and an adjustment in sensitivity relative to the new level of background light. When there is little light, the channels remain open, and calcium enters the cell.
Varnum’s lab also has shown that the ion channels are made up of two different types of building blocks or subunits. Only one is critical to the calcium-related regulation of cone sensitivity. One unusual characteristic of this subunit is that it has two equally important sites that are involved in the process.
Mutations or changes in the genes that encode the ion channels have been found to be correlated with several eye disorders, including complete achromatopsia, a disease characterized by photophobia, spasmodic eye movements, and a decreased ability to see sharp images. Varnum has determined that one of these mutations may result in making it more likely that the ion channels stay open when they should be closing.
Varnum’s lab also is interested in molecules that are physically associated with the ion channels. “The ion channels are not just lonely proteins in the membranes, out there singing the blues,” he says. The channels form partnerships with many other molecules, and Varnum is interested in how these partnerships might be important for channel activity.