scholarly journals Calcium sparks in the heart: dynamics and regulation

2015 ◽  
pp. 203 ◽  
Author(s):  
M Saleet Jafri ◽  
Aman Ullah ◽  
Tuan Hoang-Trong
Keyword(s):  
Calcium Sparks

Treatment with beta-blockers normalizes RyR2 phosphorylation and calcium spark activity in atrial myocytes from patients with atrial fibrillation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
V Jimenez-Sabado ◽  
S Casabella ◽  
P Izquierdo ◽  
C Tarifa ◽  
A Llach ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Calcium Imaging ◽  
Adrenergic Receptors ◽  
Beta Blockers ◽  
Funding Source ◽  
Atrial Myocytes ◽  
Calcium Sparks ◽  
Beta Adrenergic ◽  
Calcium Spark ◽  
Confocal Calcium Imaging

Abstract Background Atrial fibrillation has been associated with an increase in ryanodine receptor (RyR2) phosphorylation and local calcium release (calcium sparks). Carvedilol, a nonselective beta-adrenergic receptor blocker also inhibits the cardiac ryanodine receptor (RyR2), but it has been suggested that the enantiomer R-carvedilol only inhibits RyR2 activity and hence has the potential to inhibit calcium sparks without affecting RyR2 phosphorylation. Purpose This study aimed to determine the ability of the enantiomers R- and S-carvedilol to reverse RyR2 phosphorylation at s2808 and calcium sparks induced by the β2-adrenergic agonist fenoterol, in order to determine the relationship between RyR2 phosphorylation at s2808 and calcium spark frequency, and to assess the efficacy of R- and S-carvedilol. Methods Human right atrial myocytes were isolated and subjected to immunofluorescent labelling of total and s2808 phosphorylated RyR2, or loaded with fluo-4 and subjected to confocal calcium imaging. Beta-adrenergic receptors were first activated with 3μM fenoterol and then inhibited by different concentrations of carvedilol R- or S-enantiomers. Results Incubation of myocytes with fenoterol increased the s2808/RyR2 ratio from 0.32±0.03 to 0.66±0.05 (n=18, p<0.001). Incubation with 0.1, 0.3, 1 or 3μM R-carvedilol in the presence of fenoterol changed the s2808/RyR2 ratio to 0.64±0.05, 0.44±0.04, 0.34±0.07 and 0.28±0.05 (p<0.01) respectively. For comparison 3μM S-carvedilol reduced the s2808/RyR2 ratio to 0.23±0.06 in myocytes from 5 patients (p<0.01). Confocal calcium imaging revealed that fenoterol increased the spark density from 0.28±0.04 to 1.24±0.25 events/s/1000μm2 (n=9, p<0.01) and addition of 0.1, 0.3, or 1μM R-carvedilol changed the frequency to 1.32±0.52, 0.38±0.05, and 0.15±0.05 events/s/1000μm2 (p<0.01) respectively. Analysis of atrial myocytes from patients without atrial fibrillation revealed that the s2808/RyR2 ratio was similar in 25 patients treated with beta-blockers (0.39±0.04) and 57 that did not receive beta-blockers (0.44±0.03, p=0.33) while the s2808/RyR2 ratio was significantly smaller in 16 patients with atrial fibrillation receiving beta-blockers (0.43±0.08) than in 5 patients that did not (0.80±0.19, p<0.05). Conclusions R-carvedilol reverses the effects of beta-adrenergic stimulation on s2808 phosphorylation and calcium sparks in human atrial myocytes, and treatment with beta-blockers reduces excessive RyR2 phosphorylation at s2808 in patients with atrial fibrillation to levels observed in those without the arrhythmia, pointing to beta-adrenergic receptors as a target for controlling RyR2 phophorylation and activity in atrial fibrillation. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Spanish Ministry of Science and Innovation & Spanish Ministry of Health and Consume

scholarly journals Amplitude Distribution of Calcium Sparks in Confocal Images: Theory and Studies with an Automatic Detection Method

1999 ◽  
Vol 76 (2) ◽  
pp. 606-617 ◽  
Author(s):  
Heping Cheng ◽  
Long-Sheng Song ◽  
Natalia Shirokova ◽  
Adom González ◽  
Edward G. Lakatta ◽  
...  
Keyword(s):  
Detection Method ◽  
Automatic Detection ◽  
Amplitude Distribution ◽  
Calcium Sparks ◽  
Confocal Images

scholarly journals Ryanodine receptor gating controls generation of diastolic calcium waves in cardiac myocytes

2015 ◽  
Vol 145 (6) ◽  
pp. 489-511 ◽  
Author(s):  
Pavol Petrovič ◽  
Ivan Valent ◽  
Elena Cocherová ◽  
Jana Pavelková ◽  
Alexandra Zahradníková
Keyword(s):  
Ryanodine Receptor ◽  
Calcium Sensitivity ◽  
Cytosolic Calcium ◽  
Calcium Waves ◽  
Calcium Sparks ◽  
Calcium Spark ◽  
Gating Model ◽  
Calcium Diffusion ◽  
Confocal Scanning ◽  
Deterministic Description

The role of cardiac ryanodine receptor (RyR) gating in the initiation and propagation of calcium waves was investigated using a mathematical model comprising a stochastic description of RyR gating and a deterministic description of calcium diffusion and sequestration. We used a one-dimensional array of equidistantly spaced RyR clusters, representing the confocal scanning line, to simulate the formation of calcium sparks. Our model provided an excellent description of the calcium dependence of the frequency of diastolic calcium sparks and of the increased tendency for the production of calcium waves after a decrease in cytosolic calcium buffering. We developed a hypothesis relating changes in the propensity to form calcium waves to changes of RyR gating and tested it by simulation. With a realistic RyR gating model, increased ability of RyR to be activated by Ca2+ strongly increased the propensity for generation of calcium waves at low (0.05–0.1-µM) calcium concentrations but only slightly at high (0.2–0.4-µM) calcium concentrations. Changes in RyR gating altered calcium wave formation by changing the calcium sensitivity of spontaneous calcium spark activation and/or the average number of open RyRs in spontaneous calcium sparks. Gating changes that did not affect RyR activation by Ca2+ had only a weak effect on the propensity to form calcium waves, even if they strongly increased calcium spark frequency. Calcium waves induced by modulating the properties of the RyR activation site could be suppressed by inhibiting the spontaneous opening of the RyR. These data can explain the increased tendency for production of calcium waves under conditions when RyR gating is altered in cardiac diseases.

Calcium sparks in skeletal muscle fibers

Cell Calcium ◽  
2005 ◽  
Vol 37 (6) ◽  
pp. 513-530 ◽  
Author(s):  
Stephen M. Baylor
Keyword(s):  
Skeletal Muscle ◽  
Muscle Fibers ◽  
Calcium Sparks ◽  
Skeletal Muscle Fibers

scholarly journals Simultaneous Detection and Colocalization of Calcium Sparks and Ryanodine Receptor Clusters in Cardiac Myocytes

2015 ◽  
Vol 108 (2) ◽  
pp. 262a
Author(s):  
Alex Vallmitjana ◽  
Florian Hiess ◽  
S.R. Wayne Chen ◽  
Leif Hove-Madsen ◽  
Raul Benitez
Keyword(s):  
Cardiac Myocytes ◽  
Ryanodine Receptor ◽  
Simultaneous Detection ◽  
Calcium Sparks ◽  
Receptor Clusters

scholarly journals Parameter Sensitivity Analysis of Stochastic Models Provides Insights into Cardiac Calcium Sparks

2013 ◽  
Vol 104 (5) ◽  
pp. 1142-1150 ◽  
Author(s):  
Young-Seon Lee ◽  
Ona Z. Liu ◽  
Hyun Seok Hwang ◽  
Bjorn C. Knollmann ◽  
Eric A. Sobie
Keyword(s):  
Sensitivity Analysis ◽  
Stochastic Models ◽  
Parameter Sensitivity ◽  
Calcium Sparks ◽  
Parameter Sensitivity Analysis
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