S100A1 increases the gain of excitation–contraction coupling in isolated rabbit ventricular cardiomyocytes

Kettlewell, Sarah; Most, Patrick; Currie, Susan; Koch, Walter J.; Smith, Godfrey L.

doi:10.1016/j.yjmcc.2005.06.018

Cited by 67 publications

(91 citation statements)

References 29 publications

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“…Alike, recombinant S100A1 was shown to increase SR Ca 2+ release when installed through a pipette in whole-cell voltage clamped mode in rabbit CM, whereas Ca 2+ fluxes through the L-type Ca 2+ channel (I Ca ) and the sodium-calcium exchanger remained unchanged. 40 The dose-dependent increase in systolic Ca 2+ transient amplitudes further support the notion that on the one hand, S100A1 protein positively modulates the excitationcontraction coupling gain in CM, whereas on the other it is capable of attenuating the diastolic SR Ca 2+ leak.…”

Section: Exploring S100a1's Molecular and Cellular Biologysupporting

confidence: 65%

“…38 On the other hand, S100A1 was found to directly regulate RyR2 function both under systolic and diastolic conditions. 38,40,45 In experiments utilizing isolated SR vesicles, S100A1 reduced 3H-ryanodine binding to the RyR2 at about 150 nM Ca 2+ , but increased 3H-ryanodine binding at Ca 2+ levels exceeding 300 nM, pointing towards a potential biphasic effect of S100A1 on RyR2 activity. 38 Translating these findings into a functional consequence, Voelkers et al 45 demonstrated a decrease in frequency and amplitude of SR Ca 2+ sparks and waves in saponin-skinned as well as in intact quiescent normal CM employing recombinant human S100A1 protein and viral-based S100A1 overexpression, respectively.…”

Section: Exploring S100a1's Molecular and Cellular Biologymentioning

confidence: 98%

“…38 Further co-localization and co-immunoprecipitation analysis confirmed S100A1 interaction with both the sarcoplasmic reticulum Ca 2+ ATPase 2a (SERCA2a) and the ryanodine receptor 2 (RyR2), already foreshadowing its importance for SR Ca 2+ handling. [39][40][41][42] These descriptive studies were followed by a comprehensive series of functional analysis in isolated SR vesicles and in isolated CM. S100A1 was shown to interact with the SERCA2a/PLB complex in a Ca 2+ -dependent manner, thereby increasing its activity and augmenting SR Ca 2+ uptake as well as SR Ca 2+ load.…”

Section: Exploring S100a1's Molecular and Cellular Biologymentioning

confidence: 99%

“…S100A1 was shown to interact with the SERCA2a/PLB complex in a Ca 2+ -dependent manner, thereby increasing its activity and augmenting SR Ca 2+ uptake as well as SR Ca 2+ load. [38][39][40][41][42][43][44] The interaction of S100A1 with SERCA2a and the regulation of SR Ca 2+ sequestration appeared independent of PLB/SERCA2a interaction (PLB/SERCA2a ratio remained unchanged), nor interfered with PLB activation (unchanged phosphorylation at residue Serine 16 or Threonine 17) by protein kinase A (PKA) or Ca 2+ /calmodulin (CaM) -dependent protein kinase II. 44 Applying a synthetic peptide harboring the C-terminal amino-acid residues 75-94 (S100A1ct), similar results were obtained, corroborating insights into Ca 2+ -dependent conformational changes and the importance of the C-terminal extension for distinct S100A1 protein functions.…”

Section: Exploring S100a1's Molecular and Cellular Biologymentioning

confidence: 99%

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Targeting S100A1 in heart failure

Ritterhoff

Most

2012

Gene Ther

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Heart failure (HF) is the common endpoint of many cardiovascular diseases with a 1-year survival rate of about 50% in advanced stages. Despite increasing survival rates in the past years, current standard therapeutic strategies are far away from being optimal. For this reason, the concept of cardiac gene therapy for the treatment of HF holds great potential to improve disease progression, as it specifically targets key pathologies of diseased cardiomyocytes (CM). The small calcium (Ca 2+ )-binding protein S100A1 presents a promising target for cardiac gene therapy, as it has been identified as a central regulator of cardiac performance and the Ca 2+ -driven network within CM. S100A1 was shown to regulate sarcoplasmic reticulum, sarcomere and mitochondrial function by modulating target protein activity. Furthermore, deranged S100A1 expression has been linked to HF in human ischemic and dilated cardiomyopathies as well as in various HF animal models. Proof-of-concept studies in small and large animal models as wells as in human failing CM could demonstrate feasibility and efficacy of S100A1 genetically targeted therapy. This review summarizes the developmental steps of S100A1 gene therapy for the implementation into first human clinical trials.

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Section: Exploring S100a1's Molecular and Cellular Biologysupporting

confidence: 65%

Section: Exploring S100a1's Molecular and Cellular Biologymentioning

confidence: 98%

Section: Exploring S100a1's Molecular and Cellular Biologymentioning

confidence: 99%

Section: Exploring S100a1's Molecular and Cellular Biologymentioning

confidence: 99%

See 2 more Smart Citations

Targeting S100A1 in heart failure

Ritterhoff

Most

2012

Gene Ther

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“…We thus examined ARVCMs from rat hearts in which heart failure was induced using an experimental post-cryoinfarction heart failure model2627. These cells show a reduction in calcium currents compared with cells isolated from sham-operated hearts (Fig.…”

Section: Resultsmentioning

confidence: 99%

Myoscape controls cardiac calcium cycling and contractility via regulation of L-type calcium channel surface expression

et al. 2016

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Calcium signalling plays a critical role in the pathogenesis of heart failure. Here we describe a cardiac protein named Myoscape/FAM40B/STRIP2, which directly interacts with the L-type calcium channel. Knockdown of Myoscape in cardiomyocytes decreases calcium transients associated with smaller Ca2+ amplitudes and a lower diastolic Ca2+ content. Likewise, L-type calcium channel currents are significantly diminished on Myoscape ablation, and downregulation of Myoscape significantly reduces contractility of cardiomyocytes. Conversely, overexpression of Myoscape increases global Ca2+ transients and enhances L-type Ca2+ channel currents, and is sufficient to restore decreased currents in failing cardiomyocytes. In vivo, both Myoscape-depleted morphant zebrafish and Myoscape knockout (KO) mice display impairment of cardiac function progressing to advanced heart failure. Mechanistically, Myoscape-deficient mice show reduced L-type Ca2+currents, cell capacity and calcium current densities as a result of diminished LTCC surface expression. Finally, Myoscape expression is reduced in hearts from patients suffering of terminal heart failure, implying a role in human disease.

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The rapidly expanding CREC protein family: members, localization, function, and role in disease

2009

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Although many aspects of the physiological and pathophysiological mechanisms remain unknown, recent advances in our knowledge suggest that the CREC proteins are promising disease biomarkers or targets for therapeutic intervention in a variety of diseases. The CREC family of low affinity, Ca2+-binding, multiple EF-hand proteins are encoded by five genes, RCN1, RCN2, RCN3, SDF4, and CALU, resulting in reticulocalbin, ER Ca2+-binding protein of 55 kDa (ERC-55), reticulocalbin-3, Ca2+-binding protein of 45 kDa (Cab45), and calumenin. Alternative splicing increases the number of gene products. The proteins are localized in the cytosol, in various parts of the secretory pathway, secreted to the extracellular space or localized on the cell surface. The emerging functions appear to be highly diverse. The proteins interact with several different ligands. Rather well-described functions are attached to calumenin with the inhibition of several proteins in the endoplasmic or sarcoplasmic reticulum membrane, the vitamin K(1) 2,3-epoxide reductase, the gamma-carboxylase, the ryanodine receptor, and the Ca2+-transporting ATPase. Other functions concern participation in the secretory process, chaperone activity, signal transduction as well as participation in a large variety of disease processes.

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S100A1 increases the gain of excitation–contraction coupling in isolated rabbit ventricular cardiomyocytes

Cited by 67 publications

References 29 publications

Targeting S100A1 in heart failure

Targeting S100A1 in heart failure

Myoscape controls cardiac calcium cycling and contractility via regulation of L-type calcium channel surface expression

The rapidly expanding CREC protein family: members, localization, function, and role in disease

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