Ultrafast Imaging of Cardiomyocyte Contractions by Combining Scanning Ion Conductance Microscopy with a Microelectrode Array

Beating cardiomyocytes undergo fast morphodynamics during the contraction-relaxation cycle. However, imaging these morphodynamics with a high spatial and temporal resolution is difficult, owing to a lack of suitable techniques. Here, we combine scanning ion conductance microscopy (SICM) with a microelectrode array (MEA) to image the three-dimensional (3D) topography of cardiomyocytes during a contraction-relaxation cycle with 1 μm spatial and 1 ms time resolution. We record the vertical motion of cardiomyocytes at many locations across a cell by SICM and synchronize these data using the simultaneously recorded action potential by the MEA as a time reference. This allows us to reconstruct the time-resolved 3D morphology of cardiomyocytes during a full contraction-relaxation cycle with a raw data rate of 200 μs/frame and to generate spatially resolved images of contractile parameters (maximum displacement, time delay, asymmetry factor). We use the MEA-SICM setup to visualize the effect of blebbistatin, a myosin II inhibitor, on the morphodynamics of contractions. Further, we find an upper limit of 0.02% for cell volume changes during an action potential. The results show that MEA-SICM provides an ultrafast imaging platform for investigating the functional interplay of cardiomyocyte electrophysiology and mechanics.