Down-regulation of L-type calcium channel and sarcoplasmic reticular Ca2+-ATPase mRNA in human atrial fibrillation without significant change in the mRNA of ryanodine receptor, calsequestrin and phospholamban

Lai, Ling‐Ping; Su, Ming‐Jai; Lin, Jiunn Lee; Lin, Fang Yue; Tsai, Chang Her; Chen, Yih‐Sharng; Huang, Shoei K. Stephen; Tseng, Yung Zu; Lien, Wan‐Ching

doi:10.1016/s0735-1097(99)00008-x

Cited by 181 publications

(103 citation statements)

References 24 publications

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“…21 Such a finding not only indicates that the dedifferentiation process occurs only partially in fibrillating atrial myocytes but reveals GRP94 as the only SR calcium-binding protein that is increased during chronic AF, because no change was reported for calsequestrin. 7 Mechanisms responsible for the GRP94 increase in fibrillating atria remain speculative. Perturbations of ER/SR are followed by increased synthesis of GRP94, 9,10 and SR disorganization has been described within myolytic areas of fibrillating goat atrial myocytes 2 ; interestingly, a significant increase of myolysis occurred from 4 weeks of AF onward.…”

Section: Discussionmentioning

confidence: 99%

“…A thorough cytochemical analysis of calcium distribution in fibrillating goat atria showed increased sarcolemma-bound and mitochondrial calcium deposits after 1 to 2 weeks of fibrillation. 6 The increase in intracellular calcium in AF is associated with or followed by reduced accumulation of transcripts and protein for the sarcolemmal L-type Ca 2ϩ channel and SR Ca 2ϩ pump, 7,8 whereas the expression of other SR proteins involved in calcium handling, such as calsequestrin, ryanodine receptor, and phospholamban, appears to be unaffected. 7 The glucose-regulated protein GRP94 belongs to a class of stress proteins that localize in the endoplasmic reticulum (ER).…”

mentioning

confidence: 99%

“…6 The increase in intracellular calcium in AF is associated with or followed by reduced accumulation of transcripts and protein for the sarcolemmal L-type Ca 2ϩ channel and SR Ca 2ϩ pump, 7,8 whereas the expression of other SR proteins involved in calcium handling, such as calsequestrin, ryanodine receptor, and phospholamban, appears to be unaffected. 7 The glucose-regulated protein GRP94 belongs to a class of stress proteins that localize in the endoplasmic reticulum (ER). 9,10 It acts as a molecular chaperone 11 and is involved in the maintenance of cell survival because it exerts a specific protection against stresses due to Ca 2ϩ depletion from the ER.…”

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confidence: 99%

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Increased Myocardial GRP94 Amounts During Sustained Atrial Fibrillation

et al. 2001

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Background-Structural and phenotypic changes of cardiomyocytes characterize atrial fibrillation. We investigated whether changes in the glucose-regulated protein GRP94, which is essential for cell viability, occur in the presence of chronic atrial fibrillation. Methods and Results-Samples of fibrillating atrial myocardium obtained from both goat and human hearts were analyzed for GRP94 expression by an immunologic approach. In goats, atrial fibrillation was induced and maintained for 2, 4, 8, and 16 weeks. After 16 weeks of atrial fibrillation, cardioversion was applied and followed by 8 weeks of sinus rhythm. GRP94 levels doubled in goat atrial myocytes after 4 to 16 weeks of fibrillation with respect to normal atria and returned to control levels in atrial myocardium of cardioverted goats. Immunohistochemical analyses confirm that GRP94 increase occurred within cardiomyocytes. Significantly, increased levels of GRP94 were also observed in samples from human fibrillating atria. In the absence of signs of myocyte irreversible damage, the GRP94 increase in fibrillating atria is comparable to GRP94 levels observed in perinatal goat myocardium. However, calreticulin, another endoplasmic reticulum protein highly expressed in perinatal hearts, does not increase in fibrillating atria, whereas inducible HSP70, a cytoplasm stress protein that is expressed in perinatal goat hearts at levels comparable to those observed in the adult heart, shows a significant increase in chronic fibrillating atria. Conclusions-Our data demonstrate a large, reversible increase in GRP94 in fibrillating atrial myocytes, which may be related to the appearance of a protective phenotype.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Increased Myocardial GRP94 Amounts During Sustained Atrial Fibrillation

et al. 2001

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“…5,6 Moreover, a reduction in both L-type Ca 2ϩ channel mRNA and protein has been reported in patients with persistent AF. 18,19 A downregulation of calcium channels (secondary to arrhythmia-induced calcium overload) appears to be responsible for the reduction in I Ca density. 6 A reduction of the I Ca density in patients with persistent AF is expected to diminish the SR calcium loading.…”

Section: Spontaneous Sarcoplasmic Reticulum Ca 2؉ Release In Atrial Fmentioning

confidence: 99%

Atrial Fibrillation Is Associated With Increased Spontaneous Calcium Release From the Sarcoplasmic Reticulum in Human Atrial Myocytes

et al. 2004

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Background— Spontaneous Ca 2+ release from the sarcoplasmic reticulum (SR) can generate afterdepolarizations, and these have the potential to initiate arrhythmias. Therefore, an association may exist between spontaneous SR Ca 2+ release and initiation of atrial fibrillation (AF), but this has not yet been reported. Methods and Results— Spontaneous Ca 2+ release from the SR, manifested as Ca 2+ sparks and Ca 2+ waves, was recorded with confocal microscopy in atrial myocytes isolated from patients with and those without AF. In addition, the spontaneous inward current associated with Ca 2+ waves was measured with the use of the perforated patch-clamp technique. The Ca 2+ spark frequency was higher in 8 patients with AF than in 16 patients without (6.0±1.2 versus 2.8±0.8 sparks/mm per second, P <0.05). Similarly, the spontaneous Ca 2+ wave frequency was greater in patients with AF (2.8±0.5 versus 1.1±0.3 waves/mm per second, P <0.01). The spontaneous inward current frequency was also higher in 10 patients with AF than in 13 patients without this arrhythmia (0.101±0.028 versus 0.031±0.007 per second, P <0.05, at a clamped potential of −80 mV). In contrast, both the Ca 2+ released from the SR and the Na + -Ca 2+ exchange rate induced by a rapid caffeine application were comparable in patients with and without AF. Conclusions— The observed increase in spontaneous Ca 2+ release in patients with AF probably is due to an upregulation of the SR Ca 2+ release channel activity, which may contribute to the development of AF.

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“…Lower adenine nucleotides levels together with the absence of a decrease in PCr and in F 0 F 1 -ATPase activity exclude the occurrence of ischemia in this experimental model and rather documents a state of impaired energy utilization. Such metabolic changes may play a pivotal role in the perpetuation of stretch-related AF as they are tightly related to calcium handling which is known to play a key-role in AF perpetuation (39,40); calcium handling is ATP-dependent and alterations in calcium homeostasis may lead to impaired ATP synthesis (41). Putatively, an alternative mechanisms related to changes in gene expression (42) consequent to atrial mechanical stretch and yielding variations in the level of mitochondrial enzymes could have impaired ATP synthesis in our model.…”

Section: Discussionmentioning

confidence: 99%

Energetic metabolism during acute stretch-related atrial fibrillation

et al. 2008

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Background and methods-Perturbations in energetic metabolism and impaired atrial contractility may play an important role in the pathogenesis of atrial fibrillation (AF). Besides, atrial stretch is commonly associated with AF. However, the atrial energetics of stretch-related AF are poorly understood. Here, we measured indicators of energy metabolism during acute-stretch related AF. PCr, adenine nucleotides and derivatives concentrations as well as the activity of the F 0 F 1 -ATPase and Na,K-ATPase were obtained after one hour of stretch and/or AF in isolated rabbit hearts and compared to control hearts without stretch and AF.

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Down-regulation of L-type calcium channel and sarcoplasmic reticular Ca2+-ATPase mRNA in human atrial fibrillation without significant change in the mRNA of ryanodine receptor, calsequestrin and phospholamban

Abstract: L-type calcium channel and the sarcoplasmic reticular Ca(2+)-ATPase gene were down-regulated in atrial fibrillation. These changes may be a consequence of, as well as a contributory factor for, atrial fibrillation.

Cited by 181 publications

References 24 publications

Increased Myocardial GRP94 Amounts During Sustained Atrial Fibrillation

Increased Myocardial GRP94 Amounts During Sustained Atrial Fibrillation

Atrial Fibrillation Is Associated With Increased Spontaneous Calcium Release From the Sarcoplasmic Reticulum in Human Atrial Myocytes

Energetic metabolism during acute stretch-related atrial fibrillation

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