Ca 2+ release from sarcoplasmic reticulum is slowed down in heart failure

Yamamoto, Toru; Yano, Masafumi; Kohno, Michihiro; Ono, Kazunori; Hisaoka, Takayuki; Tanigawa, Taketo; Ohkusa, Toshifumi; Matsuzaki, M.

doi:10.1016/s0735-1097(98)81903-7

Cited by 2 publications

(4 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistently, previous studies have indicated that SR Ca 2+ uptake (or SERCA2a activity) is reduced in the failing animal or human myocardium (25,72,77). A decrease in the PLN mRNA level has been consistently observed in failing hearts.…”

Section: Serca2a and Plnsupporting

confidence: 87%

“…In HF, the SR Ca 2+ content is reportedly decreased (20)(21)(22) although the fraction of Ca 2+ released to Ca 2+ sequestered during Ca 2+ uptake seems to be increased (25). Both an upregulation of NCX and a reduction in SERCA2a activity may be responsible for the reduced SR Ca 2+ content observed in HF (12).…”

Section: Triggers For Ca 2+ Release and Defective E-c Coupling In Hfmentioning

confidence: 95%

“…The efficiency of the trigger (the size of the inward Ca 2+ current) needed to cause Ca 2+ release from the SR has been termed E-C coupling gain (15). In many cases of HF, the E-C coupling gain seems to be reduced by several factors: (a) a functional defect in LTCC (16)(17)(18); (b) an increase in the space between LTCC and RyR (19); (c) a decrease in SR Ca 2+ (20)(21)(22); and/or (d) an abnormality in the channel-gating property of RyR (23)(24)(25)(26). Not only the amount of Ca 2+ released for a given Ca 2+ release trigger but also the rate of Ca 2+ release may be important for the contractility of the myofilaments.…”

Section: Triggers For Ca 2+ Release and Defective E-c Coupling In Hfmentioning

confidence: 99%

See 2 more Smart Citations

Altered intracellular Ca2+ handling in heart failure

Yano

Ikeda²,

Matsuzaki³

2005

J. Clin. Invest.

187

109

View full text Add to dashboard Cite

Structural and functional alterations in the Ca 2+ regulatory proteins present in the sarcoplasmic reticulum have recently been shown to be strongly involved in the pathogenesis of heart failure. Chronic activation of the sympathetic nervous system or of the renin-angiotensin system induces abnormalities in both the function and structure of these proteins. We review here the considerable body of evidence that has accumulated to support the notion that such abnormalities contribute to a defectiveness of contractile performance and hence to the progression of heart failure. IntroductionHeart failure (HF) is characterized by a complex disorder that leads to a disturbance of the normal pumping of blood to the peripheral organs to meet the metabolic demands of the body. In a heart that has suffered myocardial damage, regardless of the initial cause of the damage (hypertension, myocardial ischemia, cardiomyopathy, etc.), HF eventually occurs if such damage persists for a prolonged period (1, 2). In the initial stages, compensation for the myocardial damage and maintenance of hemodynamics can occur via activation of both the sympathetic nervous system and the renin-angiotensin system, resulting in LV dilatation and/or hypertrophy. However, if the depressed cardiac function persists, with a parallel activation of neurohumoral factors, the myocardial damage becomes progressive and irreversible, and the heart can no longer meet the metabolic demand of the body, resulting in the phenotype of HF (1, 2).A growing body of evidence has accumulated concerning the altered intracellular Ca 2+ cycling that plays a key role in the development of HF (3-5). Recent advances in the field of molecular biology have shed light on the close relationship between Ca 2+ cycling abnormalities and the progression of HF. In many cases, altered Ca 2+ cycling precedes the observed depression of mechanical performance; consequently, an amelioration of the disorder of Ca 2+ cycling has potential as a new and intriguing therapeutic strategy against HF (5). In this review, we focus on the role of Ca 2+ regulatory proteins in the pathogenesis of HF and on the possibility of developing a new therapeutic strategy against HF using Ca 2+ regulatory proteins as the target.

show abstract

Section: Serca2a and Plnsupporting

confidence: 87%

Section: Triggers For Ca 2+ Release and Defective E-c Coupling In Hfmentioning

confidence: 95%

Section: Triggers For Ca 2+ Release and Defective E-c Coupling In Hfmentioning

confidence: 99%

See 1 more Smart Citation

Altered intracellular Ca2+ handling in heart failure

Yano

Ikeda²,

Matsuzaki³

2005

J. Clin. Invest.

187

109

View full text Add to dashboard Cite

show abstract

“…The first paper [4] showed that, in heart is responsible for a modification of SR Ca release function, failure, polylysine-induced Ca release from SR vesicles therefore causing pathophysiological changes. I would like was decreased, suggesting an impaired gating function of to discuss two points: the role of FKBP in the impairment the RYR.…”

Section: See Article By Ono Et Al [1] ( Pages 323 -331) In Thismentioning

confidence: 99%

Sarcoplasmic reticulum calcium release function and FK binding proteins in heart failure: another piece of a complex jigsaw

Terracciano

2000

Cardiovascular Research

View full text Add to dashboard Cite

See article by Ono et al. [1] ( pages 323 -331) in thisdefect in FKBP. Aspects investigated include the role of issue.the dissociation of FKBP from RYR on Ca release and the amount of FKBP in SR vesicles isolated from normal and Dysfunction is a complex phenomenon in heart failure.failing hearts. The major finding is that, in heart failure, Most cardiac structures are altered and functional relationthere is a dramatic reduction in FKBP. This corresponds to ships are disrupted. A global picture of the pathophysiolthe observation that application of the immunosuppressant ogy of heart failure is not yet available. However, many agent FK506, to produce dissociation of FKBP12.6 from studies showing modifications of different aspects of RYR in normal hearts, did not cause any further reduction cardiac physiology have been carried out and more pieces in the rate of Ca release from the SR vesicles isolated from of this complex jigsaw are revealed. Amongst these, the failing hearts. This suggests that in heart failure the paper by Ono et al., published in the present issue of regulation of FKBP on RYR is absent, resulting in Cardiovascular Research [1], focuses on the role of FK abnormal and maximal Ca leak. The authors conclude that binding proteins (FKBPs) in heart failure.the modification of the polylysine-induced SR Ca release FKBPs are immunophilin proteins associated with the in heart failure is due to a reduced amount of FKBP. SR Ca release channel (ryanodine receptor (RYR)), whichIn all three studies heart failure was induced by pacing have attracted attention because of their possible inin dogs. The authors have characterized the haemodynamic volvement in the pathophysiology of cardiac muscle. It has aspects of this model and showed a consistent systolic and been suggested that, in muscle, FKBP stabilizes RYR diastolic dysfunction of the failing hearts under invesfunction and this could be involved in the gating of the tigation. Such a model, used previously by other groups RYR [2,3]. Disruption of this binding leads to modi-(e.g [6,7]), represents a well-established technique. Howfications of the channel properties that manifest as appearever, the same authors consider some of the problems in ances of sub-conductance states and / or increased open comparing this model with the chronic failing condition probability (P ) [3]. The paper by Ono et al. [1] is the last observed in human pathophysiology.o of a trilogy from the same research group, which has Considering the evidence from this and other studies, it focused on the importance of the RYR-FKBP relationship may be concluded that in heart failure a reduction in FKBP in heart failure. The first paper [4] showed that, in heart is responsible for a modification of SR Ca release function, failure, polylysine-induced Ca release from SR vesicles therefore causing pathophysiological changes. I would like was decreased, suggesting an impaired gating function of to discuss two points: the role of FKBP in the impairment the RYR. The authors subsequently observed that ...

show abstract

Ca 2+ release from sarcoplasmic reticulum is slowed down in heart failure

Cited by 2 publications

References 0 publications

Altered intracellular Ca2+ handling in heart failure

Altered intracellular Ca2+ handling in heart failure

Sarcoplasmic reticulum calcium release function and FK binding proteins in heart failure: another piece of a complex jigsaw

Contact Info

Product

Resources

About