Abstract
This review briefly summarizes the single cell application of classical chemical dyes used to visualize cardiomyocyte physiology and their undesirable toxicities which have the potential to confound experimental observations. We will discuss, in detail, the more recent iterative development of fluorescent and bioluminescent protein-based indicators and their emerging application to cardiomyocytes. We will discuss the integration of optical control strategies (optogenetics) to augment the standard imaging approach. This will be done in the context of potential applications, and barriers, of these technologies to disease modelling, drug toxicity, and drug discovery efforts at the single-cell scale.
Highlights
The human heart contains billions of cardiomyocytes generating the repetitive force required to pump blood around the body for the lifetime of the animal
Red color variants, described as RCaMPs, have been developed but, again, the nomenclature is crowded and the reader is reminded that these are either derivatives of mRuby which was identified in the sea anemone Entacmaea quadricolor [83] or R-genetically-encoded calcium indicators for optical imaging (GECO), itself a variant of mApple, an engineered product of dsRed identified in the stony coral Discosoma sp. [84], rather than variants of the GFP from the North Pacific jellyfish Aequorea victoria that produced the GCaMPs
Bioluminescent Ca2+ indicators have been produced with improved brightness [87,88] but these probes are suitable for low frame rate applications in single cells, their conversion to dynamic calcium indicators reduces their brightness and, to date, only GeNL has been demonstrated to be effective in small clusters of iPS-CMs [88]
Summary
The human heart contains billions of cardiomyocytes generating the repetitive force required to pump blood around the body for the lifetime of the animal. Each cardiomyocyte (typically 100 μm × 20 μm × 20 μm in size) contains contractile units, called sarcomeres. These are arranged with ~2 μm spacing, contracting and relaxing 10% of that distance during each cardiac cycle. Coordinate, cardiac contraction is a hallmark of inherited and acquired disease states. Understanding this process from the single cell to whole organ scale has been a driving motivational factor for cardiovascular research. This review examines the development and application of tools to visualize how cardiomyocytes turn on, and off, in health and disease at the single-cell scale. Each topic in this review has its own literature so our aim is only to highlight tools which have proven or potential relevance to the single cardiomyocyte to provide a practical overview of how they work, and the known pitfalls in their application
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