The rhythm of the heart has been known to soothe newborns and inspire love songs. But researcher Gail Robertson is more interested in why some hearts are having trouble keeping the beat.

To Robertson, PhD, professor of neuroscience in the UW School of Medicine and Public Health, a beating heart is a physiological exercise of ion channels and cellular signaling, of contraction and circulatory regulation.

Once we understand the underlying mechanisms, we can direct therapeutic development toward those specific defects, and we can also identify through screening infants, the fetus, or an adult who may be susceptible to a sudden cardiac episode and then prevent it altogether.

“When I started as an assistant professor in the physiology department, I was studying two ion channels, both of which are derived from fruit flies. It just so happened that the physiology department was also the center of some very strong cardiovascular research,” says Robertson. “We studied the fruit fly gene in an expression system that allowed us to characterize all of its basic properties, and in doing so, we were able to link it to the human heart.”

That gene, the human Ether-a-go-go Related Gene or hERG, encodes an important ion channel - often simply referred to as a hERG channel - that mediates electrical activity of the heart and ultimately coordinates the wave of cellular activity that the average person thinks of as a heartbeat. But sometimes that channel is compromised, either by an inherited genetic mutation or by drugs.

“When the ion channels that we study are disrupted, there is a delay in the downstroke of that wave, and there can even be a reentry of some of those waves,” says Robertson. “The wave isn’t going in the direction it’s supposed to; it’s coming back on itself and can create a very dangerous condition known as ventricular fibrillation, where the heart is no longer pumping. Instead, it’s just kind of quivering, and now blood doesn’t get pumped to the brain and syncope or fainting results. If the uncoordinated waves of excitability don’t correct themselves, sudden cardiac death results.

“For reasons that we don’t yet understand, the channels that we study (hERG channels) are particularly susceptible to a wide range of drugs intended for other therapeutic targets. That’s one of the things we’re studying.”

The channels are so susceptible that in the early 1990s, the Food and Drug Administration mandated a safety test to ensure that drugs in development do not block these channels, cause a condition known as long QT syndrome, or even cause sudden cardiac death. The safety test prevents such drugs from reaching the market. In the early ’90s, before the mechanism was understood, there were several drugs that were associated with sudden cardiac death.

Defects in the ion channels that Robertson’s lab studies can not only affect children and adults, they are increasingly being associated with infant and fetal hearts. In infants, long QT syndrome is increasingly associated with Sudden Infant Death Syndrome (SIDS), and in the fetus with stillbirths. There are structural changes in the channels during development, and Robertson’s hope is that by understanding these changes, we can come to understand the vulnerabilities and the triggers that lead to cardiac arrhythmias in the very young heart.

“Once we understand the underlying mechanisms, we can direct therapeutic development toward those specific defects, and we can also identify through screening infants, the fetus, or an adult who may be susceptible to a sudden cardiac episode and then prevent it altogether,” she says.