Cardiac mechano-electric coupling research: fifty years of progress and scientific innovation.

With its conceptualisation nearly fifty years ago, cardiac mechano-electric coupling (MEC) has developed from a collection of anecdotal reports into a field of research that - in spite of early scepticism - is now an accepted part of cardiac structure-function considerations. Throughout this development, MEC studies have been both driver and beneficiary of technological innovation: from sharp electrode recordings for the study of in situ cell responses to cell isolation and patch clamp; from early approaches to mechanical stimulation of tissue using photographic diaphragms to modern force-length feedback systems for isolated cells; and from strain gauge force recordings to genetically encodes stress probes. While much is now known about subcellular contributors to cardiac MEC, including stretch-activated ion channels and mechanical modulation of cell calcium handling, their integration at higher levels of structural complexity, and the generation of clinically-translatable knowledge, have remained challenging. This short review provides a brief summary of past achievements, current activities, and potentially rewarding future directions of cardiac MEC research. We highlight challenges and opportunities on the way to an integrated understanding of how external and intrinsic mechanical factors affect the heartbeat in health and disease, and how such understanding may improve the ways in which we prevent and/or treat cardiac pathology.