Cardiac electrophysiology through 3-Photon Optical technology

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Millions of people are affected by the appearance of abnormal heartbeats, or arrhythmias- a group of conditions in which the heart beats irregularly, too fast or too slow. Arrhythmias arising in the large chambers of the heart, the ventricles, may lead to life-threatening ventricular fibrillation, an uncontrolled flutter rather than coordinated pumping or cardiac arrest. Advances in understanding the precise conditions which promote the formation of arrhythmias will be vital to the development of novel treatment strategies for at-risk patients. A key concept of cardiac function is the communication of cardiomyocytes, the excitable muscle cells of the heart, via electrical signalling impulses called action potentials. Cardiac muscle cells need to act synchronously to an initiating impulse spreading in a coordinated manner to allow blood to be efficiently pumped around the body with each beat. Conversely, when the electrical conduction between cardiomyocytes is not working properly, cardiomyocytes stop working together in a coordinated way and corresponding pumping of the entire heart at a healthy rate breaks down. Therefore, to understand the formation of arrhythmias we need understanding of the cellular electrophysiology of heart cells within their native surrounding structural environment. Since cardiac function and structure are intricately related, optical approaches are well-suited for these investigations because they are non-invasive. Using fluorescent dyes which change their light emission depending on the electrical state of the cardiomyocyte, optical microscopy techniques allow us to investigate cardiac electrical conduction with light. In this research programme, I propose to develop novel optical techniques based on 3-photon microscopy to investigate electrical activity deep within the ventricle wall beyond the reach of what is feasible with the current state of the art.