Reduced SERCA2 abundance decreases the propensity for Ca2+ wave development in ventricular myocytes

Mathis K. Stokke; Karina Hougen; Ivar Sjaastad; William E. Louch; Sarah J. Briston; Ulla H. Enger; Kristin B. Andersson; Geir Christensen; David A. Eisner; Ole M. Sejersted; Andrew W. Trafford

doi:10.1093/cvr/cvp401

Reduced SERCA2 abundance decreases the propensity for Ca2+ wave development in ventricular myocytes

Mathis K. Stokke, Karina Hougen, Ivar Sjaastad, William E. Louch, Sarah J. Briston, Ulla H. Enger, Kristin B. Andersson, Geir Christensen, David A. Eisner, Ole M. Sejersted, Andrew W. Trafford

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

Abstract

Aims: To describe the overall role of reduced sarcoplasmic reticulum Ca2+ ATPase (SERCA2) for Ca2+ wave development. Methods and results: SERCA2 knockout [Serca2flox/flox Tg(αMHC- MerCreMer); KO] mice allowing inducible cardiomyocyte-specific disruption of the Serca2 gene in adult mice were compared with Sercaflox/flox (FF) control mice. Six days after Serca2 gene disruption, SERCA2 protein abundance was reduced by 53% in KO compared with FF, whereas SERCA2 activity in field-stimulated, Fluo-5F AM-loaded cells was reduced by 42%. Baseline Ca 2+ content of the sarcoplasmic reticulum (SR) and Ca2+ transient amplitude and rate constant of decay measured in whole-cell voltage-clamped cells were decreased in KO to 75, 81, and 69% of FF values. Ca2+ waves developed in only 31% of KO cardiomyocytes compared with 57% of FF when external Ca2+ was raised (10 mM), although SR Ca 2+ content needed for waves to develop was 79% of FF values. In addition, waves propagated at a 15% lower velocity in KO cells. Ventricular extrasystoles (VES) occurred with lower frequency in SERCA2 KO mice (KO: 3 ± 1 VES/h vs. FF: 8 ± 1 VES/h) (P <0.05 for all results). Conclusion: Reduced SERCA2 abundance resulted in decreased amplitude and decay rate of Ca2+ transients, reduced SR Ca2+ content, and decreased propensity for Ca2+ wave development. © The Author 2009.

Original language	English
Pages (from-to)	63-71
Number of pages	8
Journal	Cardiovascular research
Volume	86
Issue number	1
DOIs	https://doi.org/10.1093/cvr/cvp401
Publication status	Published - Apr 2010

Keywords

Arrhythmias
Calcium waves
Delayed afterdepolarization
Excitation-contraction coupling
SERCA2

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@article{ccd8dac803274b21bac7d3ed4e6eb6eb,

title = "Reduced SERCA2 abundance decreases the propensity for Ca2+ wave development in ventricular myocytes",

abstract = "Aims: To describe the overall role of reduced sarcoplasmic reticulum Ca2+ ATPase (SERCA2) for Ca2+ wave development. Methods and results: SERCA2 knockout [Serca2flox/flox Tg(αMHC- MerCreMer); KO] mice allowing inducible cardiomyocyte-specific disruption of the Serca2 gene in adult mice were compared with Sercaflox/flox (FF) control mice. Six days after Serca2 gene disruption, SERCA2 protein abundance was reduced by 53% in KO compared with FF, whereas SERCA2 activity in field-stimulated, Fluo-5F AM-loaded cells was reduced by 42%. Baseline Ca 2+ content of the sarcoplasmic reticulum (SR) and Ca2+ transient amplitude and rate constant of decay measured in whole-cell voltage-clamped cells were decreased in KO to 75, 81, and 69% of FF values. Ca2+ waves developed in only 31% of KO cardiomyocytes compared with 57% of FF when external Ca2+ was raised (10 mM), although SR Ca 2+ content needed for waves to develop was 79% of FF values. In addition, waves propagated at a 15% lower velocity in KO cells. Ventricular extrasystoles (VES) occurred with lower frequency in SERCA2 KO mice (KO: 3 ± 1 VES/h vs. FF: 8 ± 1 VES/h) (P <0.05 for all results). Conclusion: Reduced SERCA2 abundance resulted in decreased amplitude and decay rate of Ca2+ transients, reduced SR Ca2+ content, and decreased propensity for Ca2+ wave development. {\textcopyright} The Author 2009.",

keywords = "Arrhythmias, Calcium waves, Delayed afterdepolarization, Excitation-contraction coupling, SERCA2",

author = "Stokke, {Mathis K.} and Karina Hougen and Ivar Sjaastad and Louch, {William E.} and Briston, {Sarah J.} and Enger, {Ulla H.} and Andersson, {Kristin B.} and Geir Christensen and Eisner, {David A.} and Sejersted, {Ole M.} and Trafford, {Andrew W.}",

year = "2010",

month = apr,

doi = "10.1093/cvr/cvp401",

language = "English",

volume = "86",

pages = "63--71",

journal = "Cardiovascular research",

issn = "0008-6363",

publisher = "Oxford University Press",

number = "1",

}

TY - JOUR

T1 - Reduced SERCA2 abundance decreases the propensity for Ca2+ wave development in ventricular myocytes

AU - Stokke, Mathis K.

AU - Hougen, Karina

AU - Sjaastad, Ivar

AU - Louch, William E.

AU - Briston, Sarah J.

AU - Enger, Ulla H.

AU - Andersson, Kristin B.

AU - Christensen, Geir

AU - Eisner, David A.

AU - Sejersted, Ole M.

AU - Trafford, Andrew W.

PY - 2010/4

Y1 - 2010/4

N2 - Aims: To describe the overall role of reduced sarcoplasmic reticulum Ca2+ ATPase (SERCA2) for Ca2+ wave development. Methods and results: SERCA2 knockout [Serca2flox/flox Tg(αMHC- MerCreMer); KO] mice allowing inducible cardiomyocyte-specific disruption of the Serca2 gene in adult mice were compared with Sercaflox/flox (FF) control mice. Six days after Serca2 gene disruption, SERCA2 protein abundance was reduced by 53% in KO compared with FF, whereas SERCA2 activity in field-stimulated, Fluo-5F AM-loaded cells was reduced by 42%. Baseline Ca 2+ content of the sarcoplasmic reticulum (SR) and Ca2+ transient amplitude and rate constant of decay measured in whole-cell voltage-clamped cells were decreased in KO to 75, 81, and 69% of FF values. Ca2+ waves developed in only 31% of KO cardiomyocytes compared with 57% of FF when external Ca2+ was raised (10 mM), although SR Ca 2+ content needed for waves to develop was 79% of FF values. In addition, waves propagated at a 15% lower velocity in KO cells. Ventricular extrasystoles (VES) occurred with lower frequency in SERCA2 KO mice (KO: 3 ± 1 VES/h vs. FF: 8 ± 1 VES/h) (P <0.05 for all results). Conclusion: Reduced SERCA2 abundance resulted in decreased amplitude and decay rate of Ca2+ transients, reduced SR Ca2+ content, and decreased propensity for Ca2+ wave development. © The Author 2009.

AB - Aims: To describe the overall role of reduced sarcoplasmic reticulum Ca2+ ATPase (SERCA2) for Ca2+ wave development. Methods and results: SERCA2 knockout [Serca2flox/flox Tg(αMHC- MerCreMer); KO] mice allowing inducible cardiomyocyte-specific disruption of the Serca2 gene in adult mice were compared with Sercaflox/flox (FF) control mice. Six days after Serca2 gene disruption, SERCA2 protein abundance was reduced by 53% in KO compared with FF, whereas SERCA2 activity in field-stimulated, Fluo-5F AM-loaded cells was reduced by 42%. Baseline Ca 2+ content of the sarcoplasmic reticulum (SR) and Ca2+ transient amplitude and rate constant of decay measured in whole-cell voltage-clamped cells were decreased in KO to 75, 81, and 69% of FF values. Ca2+ waves developed in only 31% of KO cardiomyocytes compared with 57% of FF when external Ca2+ was raised (10 mM), although SR Ca 2+ content needed for waves to develop was 79% of FF values. In addition, waves propagated at a 15% lower velocity in KO cells. Ventricular extrasystoles (VES) occurred with lower frequency in SERCA2 KO mice (KO: 3 ± 1 VES/h vs. FF: 8 ± 1 VES/h) (P <0.05 for all results). Conclusion: Reduced SERCA2 abundance resulted in decreased amplitude and decay rate of Ca2+ transients, reduced SR Ca2+ content, and decreased propensity for Ca2+ wave development. © The Author 2009.

KW - Arrhythmias

KW - Calcium waves

KW - Delayed afterdepolarization

KW - Excitation-contraction coupling

KW - SERCA2

U2 - 10.1093/cvr/cvp401

DO - 10.1093/cvr/cvp401

M3 - Article

C2 - 20019150

SN - 0008-6363

VL - 86

SP - 63

EP - 71

JO - Cardiovascular research

JF - Cardiovascular research

IS - 1

ER -

Reduced SERCA2 abundance decreases the propensity for Ca2+ wave development in ventricular myocytes

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Keywords

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