Tugging at the Heartstrings: The Importance and Aetiology of Cardiac Mechano-arrhythmogenesis

Feedback is an essential element of biological systems’ autoregulation, and fundamental to the adaptation of physiological activity to varying demands. A prime example is the heart – an electro-mechanical pump whose electrical excitation causes mechanical contraction of cardiomyocytes, involving a feedforward mechanism of electrically-triggered, calcium-induced calcium release from intracellular stores (‘excitation-contraction coupling’), and mechano-sensitive feedback by which the mechanical state of cardiomyocytes affects their electrical activity and calcium handling (‘mechano-electric coupling’). Although mechano-electric coupling is important for maintaining and fine-tuning normal cardiac function, it can also contribute to arrhythmias by causing aberrant electrophysiological behaviour (‘mechano-arrhythmogenesis’), particularly in cardiac diseases that alter the finely balanced physiological heterogeneity of passive and active mechanics of the heart. While the influence of mechano-electric coupling on the heart’s electrical activity is well established, the mechanisms and molecular identity of specific drivers underlying mechano-arrhythmogenesis are unclear. This seminar will describe ongoing work in our laboratory exploring the importance and aetiology of cardiac mechano-arrhythmogenesis.