S100A1 decreases calcium spark frequency and alters their spatial characteristics in permeabilized adult ventricular cardiomyocytes

Mirko Völkers; Christopher M. Loughrey; Niall MacQuaide; Andrew Remppis; Brent R. DeGeorge; Frederic v. Wegner; Oliver Friedrich; Rainer H.A. Fink; Walter J. Koch; Godfrey L. Smith; Patrick Most

doi:10.1016/j.ceca.2006.06.001

S100A1 decreases calcium spark frequency and alters their spatial characteristics in permeabilized adult ventricular cardiomyocytes

Mirko Völkers, Christopher M. Loughrey, Niall MacQuaide, Andrew Remppis, Brent R. DeGeorge, Frederic v. Wegner, Oliver Friedrich, Rainer H.A. Fink, Walter J. Koch, Godfrey L. Smith^*, Patrick Most^*

^*Corresponding author for this work

Biological and Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

56 Citations (Scopus)

Abstract

S100A1, a Ca2+-sensor protein of the EF-hand type, exerts positive inotropic effects in the heart via enhanced cardiac ryanodine receptor (RyR2) activity. Here we report that S100A1 protein (0.1microM) interacts with the RyR2 in resting permeabilized cardiomyocytes at free Ca2+-levels comparable to diastolic Ca2+-concentrations ( approximately 150nM). Alterations of RyR2 function due to S100A1 binding was assessed via analysis of Ca2+-spark characteristics. Ca2+-spark frequency, amplitude and duration were all reduced upon perfusion with 0.1microM S100A1 protein by 38%, 14% and 18%, respectively. Most likely, these effects were conveyed through the S100A1 C-terminus (S100A1-ct; amino acids 75-94) as the corresponding S100A1-ct peptide (0.1microM) inhibited S100A1 protein binding to the RyR2 and similarly attenuated frequency, amplitude and duration of Ca2+-sparks by 52%, 8% and 26%, respectively. Accordingly, the sarcoplasmic reticulum (SR) Ca2+-content was slightly increased but the stoichiometry of other accessory RyR2 modulators (sorcin/FKBP12.6) remained unaltered by S100A1. Hence, we propose S100A1 as a novel inhibitory modulator of RyR2 function at diastolic Ca2+-concentrations in rabbit ventricular cardiomyocytes.

Original language	English
Pages (from-to)	135-143
Number of pages	9
Journal	Cell Calcium
Volume	41
Issue number	2
Early online date	21 Aug 2006
DOIs	https://doi.org/10.1016/j.ceca.2006.06.001
Publication status	Published - 28 Feb 2007

Keywords

Animals
Calcium/metabolism
Calcium Signaling
Cells, Cultured
Diastole
Heart Ventricles/cytology
Myocytes, Cardiac/drug effects
Permeability
Rabbits
Ryanodine Receptor Calcium Release Channel/metabolism
S100 Proteins/metabolism
Sarcoplasmic Reticulum/metabolism

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Völkers, M., Loughrey, C. M., MacQuaide, N., Remppis, A., DeGeorge, B. R., Wegner, F. V., Friedrich, O., Fink, R. H. A., Koch, W. J., Smith, G. L., & Most, P. (2007). S100A1 decreases calcium spark frequency and alters their spatial characteristics in permeabilized adult ventricular cardiomyocytes. Cell Calcium, 41(2), 135-143. https://doi.org/10.1016/j.ceca.2006.06.001

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title = "S100A1 decreases calcium spark frequency and alters their spatial characteristics in permeabilized adult ventricular cardiomyocytes",

abstract = "S100A1, a Ca2+-sensor protein of the EF-hand type, exerts positive inotropic effects in the heart via enhanced cardiac ryanodine receptor (RyR2) activity. Here we report that S100A1 protein (0.1microM) interacts with the RyR2 in resting permeabilized cardiomyocytes at free Ca2+-levels comparable to diastolic Ca2+-concentrations ( approximately 150nM). Alterations of RyR2 function due to S100A1 binding was assessed via analysis of Ca2+-spark characteristics. Ca2+-spark frequency, amplitude and duration were all reduced upon perfusion with 0.1microM S100A1 protein by 38%, 14% and 18%, respectively. Most likely, these effects were conveyed through the S100A1 C-terminus (S100A1-ct; amino acids 75-94) as the corresponding S100A1-ct peptide (0.1microM) inhibited S100A1 protein binding to the RyR2 and similarly attenuated frequency, amplitude and duration of Ca2+-sparks by 52%, 8% and 26%, respectively. Accordingly, the sarcoplasmic reticulum (SR) Ca2+-content was slightly increased but the stoichiometry of other accessory RyR2 modulators (sorcin/FKBP12.6) remained unaltered by S100A1. Hence, we propose S100A1 as a novel inhibitory modulator of RyR2 function at diastolic Ca2+-concentrations in rabbit ventricular cardiomyocytes.",

keywords = "Animals, Calcium/metabolism, Calcium Signaling, Cells, Cultured, Diastole, Heart Ventricles/cytology, Myocytes, Cardiac/drug effects, Permeability, Rabbits, Ryanodine Receptor Calcium Release Channel/metabolism, S100 Proteins/metabolism, Sarcoplasmic Reticulum/metabolism",

author = "Mirko V{\"o}lkers and Loughrey, {Christopher M.} and Niall MacQuaide and Andrew Remppis and DeGeorge, {Brent R.} and Wegner, {Frederic v.} and Oliver Friedrich and Fink, {Rainer H.A.} and Koch, {Walter J.} and Smith, {Godfrey L.} and Patrick Most",

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doi = "10.1016/j.ceca.2006.06.001",

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T1 - S100A1 decreases calcium spark frequency and alters their spatial characteristics in permeabilized adult ventricular cardiomyocytes

AU - Völkers, Mirko

AU - Loughrey, Christopher M.

AU - MacQuaide, Niall

AU - Remppis, Andrew

AU - DeGeorge, Brent R.

AU - Wegner, Frederic v.

AU - Friedrich, Oliver

AU - Fink, Rainer H.A.

AU - Koch, Walter J.

AU - Smith, Godfrey L.

AU - Most, Patrick

N1 - Only YYYYMM date. Took last day on month. 10/06/2020 TM

PY - 2007/2/28

Y1 - 2007/2/28

N2 - S100A1, a Ca2+-sensor protein of the EF-hand type, exerts positive inotropic effects in the heart via enhanced cardiac ryanodine receptor (RyR2) activity. Here we report that S100A1 protein (0.1microM) interacts with the RyR2 in resting permeabilized cardiomyocytes at free Ca2+-levels comparable to diastolic Ca2+-concentrations ( approximately 150nM). Alterations of RyR2 function due to S100A1 binding was assessed via analysis of Ca2+-spark characteristics. Ca2+-spark frequency, amplitude and duration were all reduced upon perfusion with 0.1microM S100A1 protein by 38%, 14% and 18%, respectively. Most likely, these effects were conveyed through the S100A1 C-terminus (S100A1-ct; amino acids 75-94) as the corresponding S100A1-ct peptide (0.1microM) inhibited S100A1 protein binding to the RyR2 and similarly attenuated frequency, amplitude and duration of Ca2+-sparks by 52%, 8% and 26%, respectively. Accordingly, the sarcoplasmic reticulum (SR) Ca2+-content was slightly increased but the stoichiometry of other accessory RyR2 modulators (sorcin/FKBP12.6) remained unaltered by S100A1. Hence, we propose S100A1 as a novel inhibitory modulator of RyR2 function at diastolic Ca2+-concentrations in rabbit ventricular cardiomyocytes.

AB - S100A1, a Ca2+-sensor protein of the EF-hand type, exerts positive inotropic effects in the heart via enhanced cardiac ryanodine receptor (RyR2) activity. Here we report that S100A1 protein (0.1microM) interacts with the RyR2 in resting permeabilized cardiomyocytes at free Ca2+-levels comparable to diastolic Ca2+-concentrations ( approximately 150nM). Alterations of RyR2 function due to S100A1 binding was assessed via analysis of Ca2+-spark characteristics. Ca2+-spark frequency, amplitude and duration were all reduced upon perfusion with 0.1microM S100A1 protein by 38%, 14% and 18%, respectively. Most likely, these effects were conveyed through the S100A1 C-terminus (S100A1-ct; amino acids 75-94) as the corresponding S100A1-ct peptide (0.1microM) inhibited S100A1 protein binding to the RyR2 and similarly attenuated frequency, amplitude and duration of Ca2+-sparks by 52%, 8% and 26%, respectively. Accordingly, the sarcoplasmic reticulum (SR) Ca2+-content was slightly increased but the stoichiometry of other accessory RyR2 modulators (sorcin/FKBP12.6) remained unaltered by S100A1. Hence, we propose S100A1 as a novel inhibitory modulator of RyR2 function at diastolic Ca2+-concentrations in rabbit ventricular cardiomyocytes.

KW - Animals

KW - Calcium/metabolism

KW - Calcium Signaling

KW - Cells, Cultured

KW - Diastole

KW - Heart Ventricles/cytology

KW - Myocytes, Cardiac/drug effects

KW - Permeability

KW - Rabbits

KW - Ryanodine Receptor Calcium Release Channel/metabolism

KW - S100 Proteins/metabolism

KW - Sarcoplasmic Reticulum/metabolism

U2 - 10.1016/j.ceca.2006.06.001

DO - 10.1016/j.ceca.2006.06.001

M3 - Article

C2 - 16919727

SN - 0143-4160

VL - 41

SP - 135

EP - 143

JO - Cell Calcium

JF - Cell Calcium

IS - 2

ER -

S100A1 decreases calcium spark frequency and alters their spatial characteristics in permeabilized adult ventricular cardiomyocytes

Abstract

Keywords

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