Using biological gases to control abnormal heart rhythms
Translational Research Project Grant – Prof Derek Steele, University of Leeds
The rhythmic beating of the heart is controlled by the co-ordinated opening and closing of ‘ion channels’ in the heart cells which allow electrically charged particles – ions – to move in and out of the cells. If this electrical activity is disrupted, the resulting abnormal rhythms, called arrhythmias, may prevent the heart from pumping effectively and be life-threatening. The most common form of arrhythmia is ‘atrial fibrillation’ which is thought to affect 1-2 million people in the UK. In many cases of atrial fibrillation, the arrhythmia is partly due to a disruption of the activity of an ion channel called Kv1.5.
Most, if not all cells in the body, naturally produce gases including, surprisingly, carbon monoxide and hydrogen sulfide. These gases are well known for their toxic actions, both being highly poisonous at high levels, but in fact have important roles in controlling lots of normal processes within cells. Professor Steele and his team have discovered that both gases control the activity of the ion channel Kv1.5 and appear to protect it from disruption of its activity in atrial fibrillation.
The aim of this project is to understand how Kv1.5 is regulated by carbon monoxide and hydrogen sulfide, and how these gases protect Kv1.5 from being disrupted. The team will also manipulate the production of these gases within cells and see how this affects Kv1.5, both under normal conditions and those which mimic atrial fibrillation. This will tell us whether drugs which increase the formation of these biological gases can prevent the disruption of Kv1.5 in atrial fibrillation, and so treat this dangerous form of arrhythmia.
Atrial fibrillation dramatically increases the risk of stroke, heart failure and other life-threatening cardiac complications but current treatments are inadequate and new approaches to this common problem are needed. The ion channel Kv1.5 may represent a new target for drugs to treat this dangerous type of cardiac arrhythmia. If successful, the findings could lead to rapid development of new drugs to treat atrial fibrillation, because drugs designed to release carbon monoxide and hydrogen sulfide into the bloodstream in a controlled manner are currently under development for other conditions.