Zooming in on the Heart
"The modulation of voltage-dependent potassium channels is fascinating because it can be studied at so many different levels,” says Dr. Ming Zhou. If you met him at a party, you’d sense his enthusiasm for his work, but without specialized training, you might have trouble following exactly what he does.
After finishing his graduate and post-doctoral training, he has begun his career in research as an Assistant Professor in the Department of Physiology and Cellular Biophysics at Columbia University Medical Center.
To help understand the object of Dr. Zhou’s fascination, let’s borrow a visual metaphor from Charles and Ray Eames’ classic short film Powers of 10. We’ll zoom in and out to survey what’s happening on each level.
We’ll start by focusing on a person concerned that she or he may have a heart disorder. Cardiologists listen to the patient’s chest with a stethoscope and attach the electrodes of a heart monitor for an electrocardiogram, or EKG. The stethoscope reveals a steady lub-dub and the EKG machine a regular blip, blip, familiar from a million hospital scenes on TV.

Heart Close-Up
One of science’s most powerful techniques is reductionism: attacking a complex problem by breaking it down into smaller pieces. “I like this approach because I want to know the details,” Dr. Zhou says. So let’s zoom in to the level of individual organs where we see the heart squeezing like a fist as it pumps blood through the patient’s body: lub-dub.
Zooming in again takes us inside the heart, where sheets of muscle are nourished by a network of fine blood vessels and laced with silvery nerves that direct their action. Next, we zoom in to focus on a single muscle cell, contracting in a steady rhythm. Here is the source of the lub-dub: these contractions, synchronized among millions of similar muscle cells, create the beating of the heart.

Finding the Charge
But we still haven’t found the origin of the blip, blip. The EKG monitors electrical activity, and to understand the electrical system of the heart, we’ll need to zoom in to an individual structure within the cell’s membrane, a tiny tunnel whose mouth regularly opens and closes. This is the potassium channel Dr. Zhou studies. It opens in response to a change in the voltage across the membrane, and allows positively charged potassium ions to pour out of the cell in order to equalize the voltage again.

“Potassium channels are very important molecules in controlling the rhythmic beating of heart and channel malfunctioning leads to heart diseases.” Dr. Zhou says. “Channel functions have been studied extensively in the last 50 years and much has been learned. In a heart cell, potassium channels do not work alone because they are assembled with other proteins. As a result, there are some problems that can’t be solved by looking at the channel alone.” One such problem might happen when a blockage disrupts the supply of blood to the muscle cells. Deprived of oxygen, vital electrical cycle of the muscle cell is disrupted. The culprit here may not be the channel itself, but an associated protein called the beta subunit. Dr. Zhou’s research zooms in further, to the level of how beta subunit senses metabolic changes of a cell and fine tunes potassium channel activities.
Dr. Zhou is devoted to basic science, but his work has larger implications. If we could zoom out to our patient, we might find a problem that will soon be addressed in an innovative new way. We can see Dr. Zhou’s work as one part of the general themes of the Wu Center for Molecular Cardiology, unraveling the riddle of how malfunctions and mutations of the heart’s tiniest components lead to heart disease.
“It’s a very exciting place to be,” says Dr. Zhou.

"One of science's most powerful techniques is reductionism: attacking a complex problem by breaking it down into smaller pieces"

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