It's a complicated business that centers on the tiny channels through which potassium pours into the heart, explained Benoit G. Bruneau, an assistant professor of molecular and medical genetics at the University of Toronto, and lead author of a paper about the finding in the Oct. 21 issue of Cell.
"The main role of potassium channels is to help the heart relax after each heartbeat," Bruneau said. "But potassium channels aren't expressed the same throughout the heart. There is a slope of density, with greater density of the channels on the outside of the heart. This gradient coordinates the relaxation of the heart," he explained.
"When this gene we discovered is not present, the gradient disappears. This causes a higher propensity for arrhythmias," he said.
The discovery was made in mice that were genetically engineered to lack the gene, which the researchers have named Irx5. "What we've shown is that taking out the gene flattens the gradient," Bruneau said.
Mice are admittedly very different from humans, but the same effect has been seen in dogs, "which are very similar to humans," he said. "When we looked at dogs' hearts for the gradient effect of Irx5, indeed it was present."
Other researchers now are looking for the same effect in humans, Bruneau added.
If the human work is successful, "right now the clinical applications as far as treatment is concerned are not obvious," Bruneau said. "But as far as understanding how arrhythmias happen, this defines an important pathway, so scientists and drug companies can use it. It is a very good starting point to develop therapy. We know it might be amenable to some kind of drug treatment."
One possible therapy would be development of drugs that open and close ion channels, he said. "Another would be to modify the genetic pathway," Bruneau added.
Another possibility is that mutations in the Irx5 genes in humans can cause arrhythmias. "That is something we are investigating as well," Bruneau said.
One specific syndrome, called "short QT," which causes very severe arrhythmias and is inherited, is a leading possibility. "It resembles what we have seen in the mice," Bruneau said.
More information
You can learn about arrhythmias and how to cope with them from the American Heart Association.
