sr calcium leak
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2021 ◽  
Vol 473 (3) ◽  
pp. 363-375 ◽  
Author(s):  
Charia McKee ◽  
Dan J. Bare ◽  
Xun Ai

AbstractCalcium homeostasis in the cardiomyocyte is critical to the regulation of normal cardiac function. Abnormal calcium dynamics such as altered uptake by the sarcoplasmic reticulum (SR) Ca2+-ATPase and increased diastolic SR calcium leak are involved in the development of maladaptive cardiac remodeling under pathological conditions. Ca2+/calmodulin-dependent protein kinase II-δ (CaMKIIδ) is a well-recognized key molecule in calcium dysregulation in cardiomyocytes. Elevated cellular stress is known as a common feature during pathological remodeling, and c-jun N-terminal kinase (JNK) is an important stress kinase that is activated in response to intrinsic and extrinsic stress stimuli. Our lab recently identified specific actions of JNK isoform 2 (JNK2) in CaMKIIδ expression, activation, and CaMKIIδ-dependent SR Ca2+ mishandling in the stressed heart. This review focuses on the current understanding of cardiac SR calcium handling under physiological and pathological conditions as well as the newly identified contribution of the stress kinase JNK2 in CaMKIIδ-dependent SR Ca2+ abnormal mishandling. The new findings identifying dual roles of JNK2 in CaMKIIδ expression and activation are also discussed in this review.


2020 ◽  
Vol 118 (3) ◽  
pp. 253a
Author(s):  
Anna Fasoli ◽  
Christopher Y. Ko ◽  
Bence Hegyi ◽  
Wenjun Pan ◽  
Benjamin W. Van ◽  
...  
Keyword(s):  

2020 ◽  
Vol 118 (3) ◽  
pp. 329a
Author(s):  
Sathya Velmurugan ◽  
Amanda Hoskins ◽  
Sarah Fleischer ◽  
Florin Despa ◽  
Sanda I. Despa

2017 ◽  
Vol 112 (3) ◽  
pp. 118a
Author(s):  
Valeriy Lukyanenko ◽  
Joaquin Muriel ◽  
Robert J. Bloch

2014 ◽  
Vol 106 (2) ◽  
pp. 320a-321a
Author(s):  
George S.B. Williams ◽  
Andrew P. Wescott ◽  
W.J. Lederer ◽  
M. Saleet Jafri

2013 ◽  
Vol 104 (2) ◽  
pp. 438a
Author(s):  
Xiao Wang ◽  
Yan Hao ◽  
Seth H. Weinberg ◽  
Eric A. Sobie ◽  
Gregory D. Smith

2011 ◽  
Vol 100 (3) ◽  
pp. 557a-558a
Author(s):  
Daisuke Sato ◽  
Donald M. Bers
Keyword(s):  

2010 ◽  
Vol 588 (3) ◽  
pp. 391-392 ◽  
Author(s):  
Wei Wang ◽  
Xander H. T. Wehrens

2010 ◽  
Vol 98 (3) ◽  
pp. 509a-510a
Author(s):  
Jose M. Eltit ◽  
Jose R. Lopez ◽  
Wei Feng ◽  
Isaac N. Pessah ◽  
P.D. Allen ◽  
...  
Keyword(s):  

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Daniel P Wadsack ◽  
Michael Kohlhaas ◽  
Adam G Rokita ◽  
Stefan Neef ◽  
Lars S Maier

CaMKII is associated with hypertrophy, heart failure and alters intracellular Ca homeostasis. An increased SR Ca leak due to phosphorylation of SR Ca release channels by CaMKII leads to decreased SR Ca content and impaired contractility. This loss of Ca from the SR may also contribute to arrhythmias. We investigated whether β-adrenergic stimulation with isoproterenol (ISO) normalizes SR Ca content and whether inhibiting CaMKII reduces arrhythmias. CaMKII-overexpressing rabbit and mouse myocytes were investigated. Cell shortening, Ca fluorescence (fluo-3) and the incidence of arrhythmias were assessed. An arrhythmia-score differentiated between: early-spike-arrhythmias (ESA), late-spike-arrhythmias (LSA) and permanent arrhythmias (PA). ISO (37°C) had significantly different effects on myocytes with acute (24 h, rabbit, n=34) or chronic (22 w, mouse, n=34) CaMKII overexpression vs corresponding control myocytes (LacZ, n=21 or WT n=34). CaMKII overexpression lead to an ISO concentration-dependent (10 −10 -10 −5 mol/L) inotropic but compared to WT (or LacZ, respectively) impaired shortening and Ca transients (two-way ANOVA, P <0.05). A similar difference between CaMKII-overexpressing (n=17) and WT (n=19) myocytes was also seen during a shortening-frequency protocol (stepwise increase from 0.1– 4 Hz, two-way ANOVA, P <0.05). Arrhythmias spontaneously occurred in CaMKII-overexpressing mouse myocytes. With β-inotropic stimulation (10 −6 mol/L ISO) arrhythmias were increased 6.4-fold. Appearance of ESA and PA could be significantly reduced by KN-93 (1 μmol/L). At a basal stimulation rate of 1 Hz and 10 −7 mol/L ISO, PA could be dramatically reduced by half from control-level 21.43% (KN-92, inactive derivative, n=42) down to 10.87% (KN-93, n=46) arrhythmic events. ESA could be reduced almost 4-fold from 16.67% (KN-92) to 4.35% in the presence of KN-93. We conclude from these data that increasing ISO concentrations exerts positive inotropic effects but cannot normalize altered Ca handling in CaMKII-overexpressing myocytes. This may be due to an increased SR Ca leak under these conditions thus contributing to the arrhythmias observed. CaMKII inhibition clearly can reduce arrhythmias in the presence of β-adrenergic stimulation with ISO.


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