oa High resolution optical mapping of cardiac tissue slices: A powerful tool in heart research

Heart failure (HF) is one of the most common causes for death, to prevent HF the understanding of the (patho-)physiology is key and the development of efficient tools is an important contribution for cardiac research. Cardiac tissue slice is an increasingly popular model for cardiac electrophysiology research and pharmacological compound testing. We use optical mapping to investigate cardiac tissue slices. In this study, we perform dual imaging of trans-membrane potential (Vm) and the intracellular free calcium concentration transient (CaT) in tissue slices from the rabbit, using a relatively high spatio-temporal resolution. We detail our method for processing of the data to extract relevant characteristics of the action potential (AP) and CaT. We found that slices needed a recovery time of about 40-70 minutes after cutting, before the AP reaches a steady-state. To characterise the CaT, AP and conduction properties, we used a combination of multi-point and field stimulation, to avoid results biased by source-sink mismatches. The tight control of experimental conditions (e.g. slice 'recovery protocol' and stimulation method), leads to reproducible results, this was shown in our other studies based on using this standardised methodology [1,2]. The monitoring of multiple parameters (Vm, CaT) simultaneously at high spatial resolution (compared to patch clamp, sharp electrode, or multi-electrode arrays) allows one to study not only the properties of each parameter in a spatially detailed manner, but also the spatio-temporal interrelation between them. Especially for drug safety studies this method is superior to lower resolution methods. References: 1. Lee P, Klos M, Bollensdorff C, Hou L, Ewart P, Kamp TJ, Zhang J, Bizy A, Guerrero-Serna G, Kohl P, Jalife J, Herron TJ (2012) Simultaneous Voltage and Calcium Mapping of Genetically Purified Human Induced Pluripotent Stem Cell-Derived Cardiac Myocyte Monolayers. Circ Res 2. Lee P, Wang K, Woods CE, Yan P, Kohl P, Ewart P, Loew LM, Terrar DA, Bollensdorff C (2012) Cardiac electrophysiological imaging systems scalable for high-throughput drug testing. Pflugers Arch 464 (6):645-656. doi:10.1007/s00424-012-1149-0