3515 Increased intracellular sodium in heart failure causes reversed mode Na/Ca-exchanger dependent contribution to excitation-contraction coupling and increased fractional sarcoplasmic reticulum calcium release

2003 ◽  
Vol 24 (5) ◽  
pp. 682
Author(s):  
A BAARTSCHEER
Keyword(s):  
Heart Failure ◽  
Sarcoplasmic Reticulum ◽  
Calcium Release ◽  
Intracellular Sodium ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Sarcoplasmic Reticulum Calcium

Sarcoplasmic reticulum calcium leak and cardiac arrhythmias

2007 ◽  
Vol 35 (5) ◽  
pp. 952-956 ◽  
Author(s):  
M.G. Chelu ◽  
X.H.T. Wehrens
Keyword(s):  
Heart Failure ◽  
Sarcoplasmic Reticulum ◽  
Cardiac Arrhythmias ◽  
Ventricular Arrhythmias ◽  
Molecular Mechanisms ◽  
Calcium Release ◽  
Calcium Release Channel ◽  
Release Channel ◽  
Incomplete Closure ◽  
Sarcoplasmic Reticulum Calcium

Ventricular arrhythmias deteriorating into sudden cardiac death are a major cause of mortality worldwide. The recent linkage of a genetic form of cardiac arrhythmia to mutations in the gene encoding RyR2 (ryanodine receptor 2) has uncovered an important role of this SR (sarcoplasmic reticulum) calcium release channel in triggering arrhythmias. Mutant RyR2 channels give rise to spontaneous release of calcium (Ca2+) from the SR during diastole, which enhances the probability of ventricular arrhythmias. Several molecular mechanisms have been proposed to explain the gain-of-function phenotype observed in mutant RyR2 channels. Despite considerable differences between the models discussed in the present review, each predicts spontaneous diastolic Ca2+ leak from the SR due to incomplete closure of the RyR2 channel. Enhanced SR Ca2+ leak is also observed in common structural diseases of the heart, such as heart failure. In heart failure, defective channel regulation in the absence of inherited mutations may also increase SR Ca2+ leak and initiate cardiac arrhythmias. Therefore inhibition of diastolic Ca2+ leak through SR Ca2+ release channels has emerged as a new and promising therapeutic target for cardiac arrhythmias.

Calcium release from cardiac sarcoplasmic reticulum induced by photorelease of calcium or Ins(1,4,5)P3

1990 ◽  
Vol 258 (2) ◽  
pp. H610-H615 ◽  
Author(s):  
J. C. Kentish ◽  
R. J. Barsotti ◽  
T. J. Lea ◽  
I. P. Mulligan ◽  
J. R. Patel ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Cardiac Muscle ◽  
Calcium Release ◽  
Force Response ◽  
Cardiac Sarcoplasmic Reticulum ◽  
Excitation Contraction Coupling ◽  
Caged Compounds ◽  
Contraction Coupling ◽  
Inositol 1,4,5 Trisphosphate ◽  
Ventricular Trabeculae

The ability of Ca2+ or inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] to release Ca2+ from cardiac sarcoplasmic reticulum (SR) was investigated using saponin-skinned ventricular trabeculae from rats. To overcome diffusion delays, rapid increases in the concentrations of Ca2+ and Ins(1,4,5)P3 were produced by laser photolysis of “caged Ca2+” (Nitr-5) and “caged Ins(1,4,5)P3”. Photolysis of Nitr-5 to produce a small jump in [Ca2+] from pCa 6.8 to 6.4 induced a large and rapid force response (t1/2 = 0.89 s at 12 degrees C); the source of the Ca2+ that activated the myofibrils was judged to be the SR, since it was blocked by 0.1 mM ryanodine or 5 mM caffeine. A smaller, slower, and less consistent release of SR Ca2+ was produced by photorelease of Ins(1,4,5)P3. The results demonstrate that these caged compounds can be used to study excitation-contraction coupling in skinned multicellular preparations of cardiac muscle. The data are consistent with a major role for Ca2(+)-induced Ca2+ release in cardiac activation, whereas the role for Ins(1,4,5)P3 may be to modulate, rather than directly stimulate, SR Ca2+ release.

scholarly journals Excitation Contraction Coupling in Hypertrophy and Failing Heart Cells

2021 ◽  
Vol 271 ◽  
pp. 03008
Author(s):  
Yiqiu Zhou
Keyword(s):  
Heart Failure ◽  
Calcium Release ◽  
Heart Diseases ◽  
Calcium Handling ◽  
Heart Cells ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Failing Heart ◽  
Failure Models ◽  
And Function

The contraction of the heart is dependent on a process named the excitation-contraction coupling (E-C coupling). In hypertrophy and failing heart models, the expression, phosphorylation and function of key calcium handling proteins involved in E-C coupling are altered. It’s important to figure out the relationship changes between calcium channel activity and calcium release from sarcoplasmic reticulum (SR). This review will therefore focus on novel components of E-C coupling dysfunction in hypertrophy and failing heart, such as L-type Ca2+ channel (LCC), ryanodine receptor type-2 channel (RyR2) and SR Ca ATPase (SERCA), and how these molecular modifications altered excitation-contraction coupling. A lot of literature was well read and sorted. Recent findings in E-C coupling during hypertrophy and heart failure were focused on. Most importantly, the electrophysiological and signal pathway data was carefully analyzed. This review summarizes key principles and highlights novel aspects of E-C coupling changes during hypertrophy and heart failure models. Although LCC activity changed little, the loss of notch in action potential, reduced Ca2+ transient amplitude and desynchronized Ca2+ sparks resulted in a decreased contraction strength in hypertrophy and heart failure models. What’s more, L-type Ca2+ current becomes ineffective in triggering RyR2 Ca2+ release from SR and the SR uptake is reduced in some models. It has great meanings in understanding the E-C coupling changes during different heart diseases. Theses novel changes suggest potential therapeutic approaches for certain types of hypertrophy and heart failure.

scholarly journals Studying dyadic structure–function relationships: a review of current modeling approaches and new insights into Ca2+ (mis)handling

2017 ◽  
Vol 11 ◽  
pp. 117954681769860 ◽  
Author(s):  
Mary M Maleckar ◽  
Andrew G Edwards ◽  
William E Louch ◽  
Glenn T Lines
Keyword(s):  
Heart Disease ◽  
Sarcoplasmic Reticulum ◽  
Structure Function ◽  
Cardiac Myocytes ◽  
Calcium Release ◽  
Calcium Handling ◽  
Protein Distribution ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Calcium Dependent

Excitation–contraction coupling in cardiac myocytes requires calcium influx through L-type calcium channels in the sarcolemma, which gates calcium release through sarcoplasmic reticulum ryanodine receptors in a process known as calcium-induced calcium release, producing a myoplasmic calcium transient and enabling cardiomyocyte contraction. The spatio-temporal dynamics of calcium release, buffering, and reuptake into the sarcoplasmic reticulum play a central role in excitation–contraction coupling in both normal and diseased cardiac myocytes. However, further quantitative understanding of these cells’ calcium machinery and the study of mechanisms that underlie both normal cardiac function and calcium-dependent etiologies in heart disease requires accurate knowledge of cardiac ultrastructure, protein distribution and subcellular function. As current imaging techniques are limited in spatial resolution, limiting insight into changes in calcium handling, computational models of excitation–contraction coupling have been increasingly employed to probe these structure–function relationships. This review will focus on the development of structural models of cardiac calcium dynamics at the subcellular level, orienting the reader broadly towards the development of models of subcellular calcium handling in cardiomyocytes. Specific focus will be given to progress in recent years in terms of multi-scale modeling employing resolved spatial models of subcellular calcium machinery. A review of the state-of-the-art will be followed by a review of emergent insights into calcium-dependent etiologies in heart disease and, finally, we will offer a perspective on future directions for related computational modeling and simulation efforts.

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