Relevance of cardiomyocyte mechano-electric coupling to stretch-induced arrhythmias: optical voltage/calcium measurement in mechanically stimulated cells, tissues and organs.

Stretch-induced arrhythmias are multi-scale phenomena in which alterations in channel activities and/or calcium handling lead to the organ level derangement of the heart rhythm. To understand how cellular mechano-electric coupling (MEC) leads to stretch-induced arrhythmias at the organ level, we developed stretching devices and optical voltage/calcium measurement techniques optimized to each cardiac level. This review introduces these experimental techniques of (1) optical voltage measurement coupled with a carbon-fiber technique for single isolated cardiomyocytes, (2) optical voltage mapping combined with motion tracking technique for myocardial tissue/whole heart preparations and (3) real-time calcium imaging coupled with a laser optical trap technique for cardiomyocytes. Following the overview of each methodology, results are presented. We conclude that individual MEC in cardiomyocytes can be heterogeneous at the ventricular level, especially when moderate amplitude mechanical stretches are applied to the heart, and that this heterogeneous MEC can evoke focal excitation that develops into re-entrant arrhythmias.