Excitation–Contraction Coupling of Cardiomyocytes

Kockskämper, Jens

doi:10.1007/978-3-319-31251-4_3

Cited by 3 publications

(3 citation statements)

References 145 publications

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“…In the heart, Ca 2+ most prominently mediates the translation of electrical stimulation into the mechanical activity of cardiomyocytes—also known as excitation-contraction coupling (ECC)—thus inducing the contraction of cardiac muscle [ 2 ]. Each heartbeat is characterized by a precisely regulated transient rise in cytoplasmic free Ca 2+ to systolic levels of about 1 µM at peak contraction and subsequent removal to diastolic levels of about 100 nM at full relaxation [ 3 , 4 ]. Beyond this well-described role in cardiomyocyte contractile function, Ca 2+ has emerged as a key player in both physiological and pathophysiological cardiac signaling cascades and the regulation of gene transcription.…”

Section: Introductionmentioning

confidence: 99%

Nuclear Calcium in Cardiac (Patho)Physiology: Small Compartment, Big Impact

et al. 2023

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The nucleus of a cardiomyocyte has been increasingly recognized as a morphologically distinct and partially independent calcium (Ca2+) signaling microdomain, with its own Ca2+-regulatory mechanisms and important effects on cardiac gene expression. In this review, we (1) provide a comprehensive overview of the current state of research on the dynamics and regulation of nuclear Ca2+ signaling in cardiomyocytes, (2) address the role of nuclear Ca2+ in the development and progression of cardiac pathologies, such as heart failure and atrial fibrillation, and (3) discuss novel aspects of experimental methods to investigate nuclear Ca2+ handling and its downstream effects in the heart. Finally, we highlight current challenges and limitations and recommend future directions for addressing key open questions.

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Section: Introductionmentioning

confidence: 99%

Nuclear Calcium in Cardiac (Patho)Physiology: Small Compartment, Big Impact

et al. 2023

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“…Typical stress reactions involve the expression of cold or heat shock proteins, which can adversely affect vital cell functions [10]- [12]. Hypothermia/rewarming (H/R) cycles are known to reduce myofilament Ca 2+ sensitivity and affect cardiac action potentials (AP) and contractility [13], [14]. They have also been shown to affect the sarcomere length and cardiac muscle force generation in animal models [14]- [16].…”

Section: Introductionmentioning

confidence: 99%

Cardiomyocytes: Analysis of Temperature Response and Signal Propagation Between Dissociated Clusters Using Novel Video-Based Movement Analysis Software

et al. 2020

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Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) provide a great resource for functional cell and tissue models that can be applied in heart research, pharmaceutical industry, and future regenerative medicine. During cell model experiments, precise control of environmental parameters is important. Temperature is a fundamental parameter, and the acute effect of temperature on hiPSC-CM functions has previously been studied. This paper reports on long-term, systematic temperature response studies of hiPSC-CM cultures. The studies were conducted outside an incubator in a modular cell culturing system along with a temperature sensor plate (TSP) and a new beating analysis software (CMaNcardiomyocyte function analysis tool). Temperature sensing at the actual cell location is challenging with bulky external sensors; however, a TSP with resistive microsensors provides an effortless solution. Experimental results showed that temperature nonlinearly affects the hiPSC-CM beating frequency with a Q10 temperature coefficient of ~2.2. Both the active (contraction) and passive (relaxation) movements were influenced by temperature, and changes in the relaxation times were larger than the contraction times. However, the contraction amplitudes exhibited a greater spread of variation. We also present novel results on the visualization of hiPSC-CM contractile networking and non-invasive image-based measurement of signal propagation between dissociated CM clusters. Compared with previously reported tools, CMaN is an advanced and easy-to-use robust software. It is faster, more sensitive, computationally less expensive, and extracts six different signals of the contractile motion per process, providing at least one useful beating signal even in complex cases. The software also supports movement center detection and independent computation of the relaxation and contraction parameters.

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“…In cardiac muscle, Ca constitutes a key player in excitation-contraction coupling (ECC), linking electrical stimulation to mechanical contraction. During each heartbeat free intracellular Ca concentration rises to a systolic level of ∼1 μM enabling interaction between the contractile filaments, followed by Ca removal to a diastolic level of ∼100 nM causing relaxation (Bers, 2001; Kockskämper, 2016). Besides the well characterized functions of cytosolic Ca in driving the contraction-relaxation cycle in ECC, more recent studies have revealed the role of Ca in controlling gene transcription in cardiac myocytes in a process termed excitation-transcription coupling (ETC) (Wu et al, 2006; Dewenter et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

SERCA Activity Controls the Systolic Calcium Increase in the Nucleus of Cardiac Myocytes

Kiess

Kockskämper

2019

Front. Physiol.

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In cardiomyocytes, nuclear calcium is involved in regulation of transcription and, thus, remodeling. The cellular mechanisms regulating nuclear calcium, however, remain elusive. Therefore, the aim of this study was to identify and characterize the factors that regulate nuclear calcium in cardiomyocytes. We focused on the roles of (1) the cytoplasmic calcium transient (CaT), (2) the sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA), and (3) intracellular calcium stores for nuclear calcium handling. Experiments were performed on rat ventricular myocytes loaded with Fluo-4/AM. Subcellularly resolved CaTs were visualized using confocal microscopy. The cytoplasmic CaT was varied by reducing extracellular calcium (from 1.5 to 0.3 mM) or by exposure to isoprenaline (ISO, 10 nM). SERCA was blocked by thapsigargin (5 μM). There was a strict linear dependence of the nucleoplasmic CaT on the cytoplasmic CaT over a wide range of calcium concentrations. Increasing SERCA activity impaired, whereas decreasing SERCA activity augmented the systolic calcium increase in the nucleus. Perinuclear calcium store load, on the other hand, did not change with either 0.3 mM calcium or ISO and was not a decisive factor for the nucleoplasmic CaT. The results indicate, that the nucleoplasmic CaT is determined largely by the cytoplasmic CaT via diffusion of calcium through nuclear pores. They identify perinuclear SERCA activity, which limits the systolic calcium increase in the nucleus, as a novel regulator of the nuclear CaT in cardiac myocytes.

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Excitation–Contraction Coupling of Cardiomyocytes

Cited by 3 publications

References 145 publications

Nuclear Calcium in Cardiac (Patho)Physiology: Small Compartment, Big Impact

Nuclear Calcium in Cardiac (Patho)Physiology: Small Compartment, Big Impact

Cardiomyocytes: Analysis of Temperature Response and Signal Propagation Between Dissociated Clusters Using Novel Video-Based Movement Analysis Software

SERCA Activity Controls the Systolic Calcium Increase in the Nucleus of Cardiac Myocytes

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