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Quantitative Super-Resolution Microscopy of Cardiomyocytes

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Microscopy of the Heart

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Abstract

Cardiomyocytes are among the largest of animal cell types. At ~20 μm in typical width and ~100 μm in length, these cells are intrinsically organised to contract rapidly and in synchrony in response to electrical activation. This excitation-contraction coupling (EC coupling) process is achieved through the synchronised opening of the primary calcium (Ca2+) release channels of the sarcoplasmic reticulum (SR)—the ryanodine receptors (RyRs) [1]. A series of tubular membrane invaginations of the surface sarcolemma, known as the t-tubules, are the primary sites of this Ca2+ release deeper within the cell where RyRs are organised into clusters in quasi-crystalline patterns [2, 3]. Flanked between the t-tubule membrane and the SR membrane at the dyadic cleft, the cytoplasmic portions of these giant (29 nm × 29 nm) Ca2+ channel [4] are opened by the Ca2+ that enters the cleft through the voltage-gated L-type Ca2+ channel (LCC). This process, known as Ca2+ induced Ca2+ release (CICR) crucially relies on the restricted diffusion and the consequently elevated concentration of the cleft Ca2+ [5]. Described in the theory of local control of EC coupling, the Ca2+ released via RyRs is likely a steep function of the dimensions of the dyadic cleft and the trigger Ca2+ concentration [6]. The synchronisation of the contraction also relies heavily on the effectiveness of this Ca2+ in reaching and activating the contractile machinery (which forms the myofibrils). Early light and electron micrographs have demonstrated that t-tubules and dyads are, to this end, organised all around the myofibrils to minimise the typical diffusional distance of the released calcium [7–10].

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Authors and Affiliations

  1. Living Systems Institute, University of Exeter, Exeter, UK

    Christian Soeller

  2. Department of Physiology, University of Auckland, Auckland, New Zealand

    Christian Soeller

  3. Biomedical Physics, University of Exeter, Exeter, UK

    Izzy D. Jayasinghe

  4. School of Biomedical Sciences, University of Leeds, Leeds, UK

    Izzy D. Jayasinghe

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  1. Christian Soeller
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Correspondence to Christian Soeller .

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  1. Theoretical Medicine and Biosciences, Saarland University, Homburg/Saar, Germany

    Lars Kaestner

  2. Preclinical Center for Molecular Signal Processing, Building 61, Saarland University, Homburg/Saar, Germany

    Peter Lipp

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Soeller, C., Jayasinghe, I.D. (2018). Quantitative Super-Resolution Microscopy of Cardiomyocytes. In: Kaestner, L., Lipp, P. (eds) Microscopy of the Heart. Springer, Cham. https://doi.org/10.1007/978-3-319-95304-5_3

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