University of Oxford, UK

A physiologist discusses matters close to the heart.

This time last year my father was suffering from congestive heart failure. He became increasingly frail, slowing down like an unwound clockspring until, in February, his heart simply stopped.

As a physiologist, I had some idea of his condition, but I did not then realize how close it was to my own research area.

In 1983, ATP-sensitive potassium (K-ATP) channels were found in the heart. These channels are gated pores that control potassium fluxes across the cell membrane. However, their precise role in the heart was unclear.

One year later, I discovered that these channels are central to the mechanism by which glucose stimulates insulin secretion from the pancreas. Unravelling the role of K-ATP channels in diabetes, and the way in which channel structure influences function, has been an all-consuming passion for me ever since.

To my surprise, it now turns out that these channels also play a role in heart failure. Heart failure is usually caused by narrowing of the arteries, which increases the pressure against which the heart has to pump, making it work harder. Eventually, it fails.

Recently, Andre Terzic of the Mayo Clinic in Rochester, Minnesota, and his group showed that K-ATP channels confer protection against heart failure (S. Yamada et al. J. Physiol. Lond. published online doi:10.1113/jphysiol.2006.119511; 2006). In normal mice, cardiac K-ATP channels open in response to an increased pressure load, reducing stress on the heart. Mice lacking K-ATP channels rapidly develop heart failure and die.

In the pancreas, K-ATP-channel activity is finely balanced: too much causes diabetes and too little hyperinsulinism. But in the heart, as this paper shows, opening is almost always beneficial.