How do faults in the calmodulin gene cause dangerous arrhythmias?

CALM HEART. Investigating the role of calmodulin in cardiac arrhythmia

Many heart conditions run in families because they are caused by a fault or variation in our genetic code that is inherited through the generations. Some genetic faults increase the risk of developing irregular heartbeats – known as arrhythmias – in conditions such as Long QT Syndrome. These disrupted heart rhythms affect people of all ages and can be life-threatening. More effective ways to prevent or control inherited arrhythmias are needed, so researchers are on a quest to uncover and tackle the molecular processes at the heart of these conditions. Recent studies of people with inherited arrhythmias have identified faults in a gene that holds the instructions to make a protein called ‘calmodulin’ (CaM). This suggests that when CaM does not work correctly, arrhythmias can develop. CaM is important for balancing calcium levels within the cells of the heart, and when this balance is upset, it can lead to the development of arrhythmias. However, how faults in CaM lead to irregular heartbeats in these heart diseases is unclear. Dr Helassa will investigate why these faulty versions of CaM affect the heartbeat by examining in detail how they are different from the normal CaM. These studies will help us better understand how inherited arrhythmias occur. They will shine a light on new avenues for drug design to improve treatment of these dangerous heart diseases.