Understanding how gene mutations cause arrhythmia

Disease modelling of the POPDC1S201F and the POPDC2W188X mutations associated with cardiac arrhythmia

When we exercise, increased amounts of adrenaline circulate in our body stimulating the heart to beat faster. Adrenaline works by stimulating another molecule called cyclic AMP (cAMP) which is recognised by protein molecules in heart cells. This project focuses on a class of these molecules called POPDC proteins. People who have mutations in POPDC1 and POPDC2 genes can develop an irregular heart beat or contraction (called arrhythmia) in response to stress or physical activity. However, it is not fully understood why these arrhythmias occur. To investigate this, Professor Brand and his team have engineered a mouse to carry the same mutation seen in some people with arrhythmia. They will study heart function in the mice using electrocardiogram (ECG) analysis and will look at how the mutation affects the behaviour of ion channels. These are transporter molecules on the surface of cells that allow substances in and out and play an essential role in the heart muscle’s ability to contract. This project will help better understanding of the why these mutations cause arrhythmia, which might also help to develop novel treatment strategies for people with arrhythmia linked by POPDC mutations.