Contact: Michael Varnum, 509-335-0701, varnum@wsu.edu
As you read this, thank your ion channels
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.