"Sodium channels are the fastest ion channels in the human body and are needed to experience nearly every sensation, so mutations in them can lead to severe disorders of the nerves, muscles and heart," Bosmans says. That makes them a critical target for scientific study.
To understand the channels better, Bosmans and his team insert the protein's gene into frog eggs, which are large and easy to study. They can then use electrodes to monitor the flow of sodium into the cells. Adding spider toxins that interfere with the function of the channels sheds light on the channels' activity, since different toxins inhibit different parts of the protein, causing different effects. In addition to testing human sodium channels, the team sometimes works with sodium channels from insects.
Because his laboratory recently acquired the gene for the German cockroach sodium channel, Bosmans' team tested Dc1a on the protein and saw a startling increase in the channels' activity. "Sodium poured into the cells. In a bug, that would cause massive seizures, much like being electrocuted," says Bosmans. "Luckily, the toxin doesn't act on human sodium channels."
Curious about the difference between the two cockroach species' channels, they first identified the region of the channel that the toxin targets, but it turned out to be exactly the same in the two bugs. Digging deeper, they found a region nearby that differed by just two amino acids, the basic building blocks of the proteins. When mutations were made in the German version so that its amino acids were the same as the American version's, the German cockroach sodium channel reacted like the American one.
The team's next step is to test the toxin on other insect species to determine its full range. Now that they know how important this region of sodium chann
|Contact: Catherine Kolf|
Johns Hopkins Medicine