Characterising calcium control in atrial fibrillation

The cardiac sarcoplasmic reticulum in health and disease: new mechanisms and novel ion-channels

Atrial fibrillation (AF), a common heart rhythm disturbance, is a major risk factor for having a stroke, as well as causing shortness of breath and dizziness in patients. In AF, the heartbeat becomes irregular. The exact causes are not well understood but the role of calcium as a messenger between heart cells is known to be important in maintaining normal function of the heart. Levels of calcium in the heart are carefully controlled during the coordinated cycle of a heartbeat. At the correct time during initiation of a heartbeat, calcium is released from a special storage structure in heart cells called the sarcoplasmic reticulum. The calcium flows through special pores or channels in this structure. However, the behaviour of these channels is complex and poorly understood. In conditions such as AF, heart rhythm is affected by too much calcium leaking out through the channels into the heart. Dr Rebecca Sitsapesan and Dr Krasimira Tsaneva-Atanasovo, from the University of Bristol, are looking in-depth at calcium control in heart cells. In collaboration with a worldwide team including scientists from the USA and Japan, they will study how the channels in the sarcoplasmic reticulum work together in harmony to control calcium release. Drs Sitsapesan and Tsaneva-Atanasovo are particularly interested in a calcium channel called TRIC-A. The duo very recently became the first team to fully characterise the function and structure of TRIC-A. Now with the help of BHF funding, they will be looking at what may happen when TRIC-A goes wrong, and also investigate how it interacts with other protein channels which seem to be important in controlling a normal heartbeat. Understanding the characteristics of protein channels such as TRIC-A is vital to identify potential new treatments that can target and correct the action of damaged channels.