University At Buffalo Biophysicists Develop New Software That Makes Fast Ion-Channel Analysis Possible

BUFFALO, N.Y. -- The interpretation of the activity of ion channels -- the protein structures that regulate the flow of electrical current in cells -- can be so difficult and time-consuming that many researchers have simply given up on it.

But comprehending the properties of ion channels, which control the activity of the bodyâs organs, including the brain, is key to understanding normal physiology. It also is critical to understanding various genetic diseases, including cystic fibrosis, as well as some neuromuscular disorders and some cardiac arrythmias.

Now, biophysicists at the University at Buffalo have developed software programs that can perform ion-channel analysis with remarkable efficiency and speed.

The researchers have received a four-year, $1 million grant from the National Institutes of Health to enhance the programs and to move them from the current UNIX environment to Windows.

The current version of the software may be downloaded from the World Wide Web at http://barrel.med.buffalo.edu

ãOur software makes analyzing ion channels so much easier and faster that researchers will be able to try things that were too painfully slow to even try before, said Frederick Sachs, Ph.D., professor of biophysical sciences at UB and principal investigator. Co-investigators are Anthony L. Auerbach, Ph.D., associate professor of biophysical sciences at UB, and Qin Feng, Ph.D., postdoctoral research fellow.

With the new software programs, named QUB, a researcher can discover in minutes how long it takes for an ion channel to change from one conformation to another. Previously, such measurements could have taken months.

According to the UB researchers, this information will provide biophysicists with a powerful tool useful for both basic and applied research.

Sachs explained that better information on these proteins could make a tremendous difference in drug design, particularly for conditions where ion channels are implicated.

ãFor example, in people who have some kinds of inherited neuromuscular diseases, an amino acid in the receptors for the neurotransmitter has been altered, he said.

These alterations cause the ion channels either to stay open too long or not long enough, resulting in clinical disorders where the muscles are either too weak or too excitable.

By analyzing the currents that are produced by the ion channels that bind the transmitter, scientists have been able to tell which part of the channel operation is affected and suggest possible treatments.

QUB also is expected to be a boon to researchers who want to study protein dynamics in general. Since the flow of current through a channel makes many of the conformational states of ion channels visible, it is possible to see kinetic details that in most proteins are invisible.

ãAn ion channel can pass more than 1 million ions per second,' Sachs said. That's a big enough output to measure in real time. The programs allow you to not only Îwatchâ an ion channel molecule at work, they provide specific quantitative results on how it works, on how fast protein molecules change shape.

That information will give scientists a critical window into a protein's four-dimensional structure (in space and time), which determines its function, he explained.

The software uses algorithms based on the work of Russian mathematician Andrey Andreyevich Markov, similar to those currently used by computers to convert speech and handwriting to text.

It analyzes data obtained from experiments in which the electrical current produced by the ion channel in a cell is monitored and amplified.

That information is then fed to the computer.

The program then allows the researcher to develop accurate models of ion-channel behavior based on the experimental data.

The program says, "Give me a dataset and the models that you think apply, said Sachs. It then calculates which of the models provides the most likely explanation for the data and how much confidence to have in the results. It summarizes millions and even billions of experimental data points into a few constants and it will do it in about a minute.