VCU researchers study the molecular underpinnings of what makes the heart tick

By Sathya Achia Abraham

A team of Virginia Commonwealth University researchers is studying cells found in the heart to determine the underlying causes of abnormal heart rhythms – those acquired and those due to genetic factors.

Gea-Ny Tseng, Ph.D., professor of physiology and biophysics in the VCU School of Medicine, hopes that her work may help researchers develop drugs that can target specific molecular regions in heart cells to treat patients with acquired or congenital arrhythmias.

Tseng and a VCU research team, together with investigators from Columbia University in New York, Shiga University of Medical Science in Japan and Tonji Medical College of Huazhong University of Science and Technology in China, have been working to better understand how ion channels in heart cells function and regulate the heart.

In the human heart, the slow delayed rectifier channel, or IKs, is one of the major ion channels responsible for regulating the organ’s action potential configuration and duration.

According to Tseng, heart cells constantly go through excitation-resting cycles. In the resting phase of the cycle, the heart is in a relaxed state and the chambers are being filled with blood. In the excitation phase of the cycle, the heart is in a contractile state to pump the blood into vessels.

“Action potentials are responsible for initiating the excitation/contractile state. The shape or configuration, and the duration of action potentials need to be tightly regulated by hormones, neurotransmitters and many other factors, so that the heart can exert appropriate force to pump the blood in a synchronized fashion,” explained Tseng.

In a study published in the June 12 issue of The Journal of Biological Chemistry, the team reported that cells in the heart may dynamically regulate the current amplitude of the IKs channel in response to their changing environment so that they can produce appropriate electrical and mechanical outputs to support the rhythmic activity and pump function of the heart. This is achieved by IKs regulating the action potential configuration and duration.

Tseng said that the team continues to build on this research. They are investigating how conditions of the heart such as aging, chronic hypertension and myocardial infarction can impact the ion channels. They are also studying the molecular mechanisms of these ion channels, and specifically where these proteins bind to each other. The team plans to build 3-D molecular structures of the ion channels, which will be helpful in the drug discovery process and help determine potential target compounds that can interrupt interactions of these channels and potentially prevent arrhythmias.

This work was supported by grants from the National Heart, Lung and Blood Institute.