The Hubbub About the Heart’s Lub-Dub

Love isn’t the only phenomenon that can make the heart skip a beat.

Brandeis scientists have shed light on a blueprint of key heart structures that help regulate contractions. Unraveling how these proteins, called potassium ion channels, are built is essential to understanding and developing treatments for arrhythmias and other life-threatening heart conditions.

For years, scientists have debated how many membrane proteins are required to build one of these channels, theorizing they could number anywhere between one and 14. In a report published earlier this year in the Proceedings of the National Academy of Sciences, Brandeis researchers challenged a previous study, the findings of which are currently being used in drug development trials and animal models.

Each slow expansion and contraction of heart muscle is a heartbeat. To make the beat go on, a series of channels on the surface of heart cells help regulate the movement of different ions into and out of the cells.

The potassium ion channel, made up of the proteins Q1 and E1, is critical to ending each heart contraction. Q1s create the pore that the potassium flows through, and the E1s control how slowly that pore opens and closes, how many channels are on the surface of each cell and how they are regulated by drugs.

Leigh Plant, assistant research professor of biochemistry, along with postdoctoral fellows Dazhi Xiong and Hui Dai, and provost and professor of biochemistry Steve Goldstein ’78, MA’78, discovered that two E1s and four Q1s are in each channel.

Goldstein’s team observed E1 in live mammalian cells at remarkable sensitivity, counting the proteins in individual channels, something that had never been done before (a channel is 100,000 times smaller than the period at the end of this sentence). Because the issue has been widely debated, Goldstein and his team used three different means to count E1s — including tagging them with different fluorescent colors and using a scorpion toxin to bind to Q1. Each time, the team got the same results.

The researchers believe their new findings may help create more effective models to study heart conditions and their treatment.

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