ArticleThe Journal of physiology2011
Regulation of sarcoplasmic reticulum Ca²⁺ leak by cytosolic Ca²⁺ in rabbit ventricular myocytes.
Article in The Journal of physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- Restoration of mitochondrial CaJournal of molecular and cellular cardiology · 2026Article
- Role of ryanodine receptor cooperativity in CaThe Journal of physiology · 2024Article
- Estimating ectopic beat probability with simplified statistical models that account for experimental uncertainty.PLoS computational biology · 2021Article
- TRIC-A regulates intracellular CaPflugers Archiv : European journal of physiology · 2021Review
- Magnesium Ions Moderate Calcium-Induced Calcium Release in Cardiac Calcium Release Sites by Binding to Ryanodine Receptor Activation and Inhibition Sites.Frontiers in physiology · 2021Article
- A compartmentalized mathematical model of mouse atrial myocytes.American journal of physiology. Heart and circulatory physiology · 2020Article
- Impaired Activity of Ryanodine Receptors Contributes to Calcium Mishandling in Cardiomyocytes of Metabolic Syndrome Rats.Frontiers in physiology · 2019Article
- Late CaCirculation research · 2018Article
- Ambiguous interactions between diastolic and SR CaThe Journal of general physiology · 2017Review
- Systolic [CaThe Journal of physiology · 2017Article
- The effect of PKA-mediated phosphorylation of ryanodine receptor on SR CaJournal of molecular and cellular cardiology · 2017Article
- Importance of Altered Levels of SERCA, IPBiophysical journal · 2017Article
- Late INa increases diastolic SR-Ca2+-leak in atrial myocardium by activating PKA and CaMKII.Cardiovascular research · 2015Article
- Junctional cleft [Ca²⁺]i measurements using novel cleft-targeted Ca²⁺ sensors.Circulation research · 2014Article
- Ca handling during excitation-contraction coupling in heart failure.Pflugers Archiv : European journal of physiology · 2014Review
- Mechanisms of Ca²+ handling in zebrafish ventricular myocytes.Pflugers Archiv : European journal of physiology · 2013Article
- Ryanodine receptors, calcium signaling, and regulation of vascular tone in the cerebral parenchymal microcirculation.Microcirculation (New York, N.Y. : 1994) · 2013Review
- Posttranslational modifications of cardiac ryanodine receptors: Ca(2+) signaling and EC-coupling.Biochimica et biophysica acta · 2013Review
- Modulation of intracellular calcium waves and triggered activities by mitochondrial ca flux in mouse cardiomyocytes.PloS one · 2013Article
- Facilitation of cytosolic calcium wave propagation by local calcium uptake into the sarcoplasmic reticulum in cardiac myocytes.The Journal of physiology · 2012Article
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4 authors at 2 institutions in 1 country.
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Abstract
Sarcoplasmic reticulum (SR) Ca(2+) leak determines SR Ca(2+) content and, therefore, the amplitude of global Ca(2+) transients in ventricular myocytes. However, it remains unresolved to what extent Ca(2+) leak can be modulated by cytosolic [Ca(2+)] ([Ca(2+)](i)). Here, we studied the effects of [Ca(2+)](i) on SR Ca(2+) leak in permeabilized rabbit ventricular myocytes. Using confocal microscopy we monitored SR Ca(2+) leak as the change in [Ca(2+)](SR) (with Fluo-5N) after complete SERCA inhibition with thapsigargin (10 μm). Increasing [Ca(2+)](i) from 150 to 250 nM significantly increased SR Ca(2+) leak over the entire range of [Ca(2+)](SR). This increase was associated with an augmentation of both Ca(2+) spark- and non-spark-mediated Ca(2+) leak. Further increasing [Ca(2+)](i) to 350 nM led to rapid [Ca](2+)](SR) depletion due to the occurrence of Ca(2+) waves. The augmentation of SR Ca(2+) leak by high [Ca(2+)](i) was insensitive to inhibition of Ca(2+)-calmodulin-dependent protein kinase II. In contrast, lowering [Ca(2+)](i) to 50 nM markedly decreased SR Ca(2+) leak rate and nearly abolished Ca(2+) sparks. When the ryanodine receptor (RyR) was completely inhibited with ruthenium red (50 μM), changes in [Ca(2+)](i) between 50 and 350 nM did not produce any significant effect on SR Ca(2+) leak, indicating that [Ca(2+)](i) alters SR Ca(2+) leak solely by regulating RyR activity. In summary, [Ca(2+)](i) in the range of 50-350 nM has a significant effect on SR Ca(2+) leak rate mainly via direct regulation of RyR activity. As RyR activity depends highly on [Ca(2+)](i) and [Ca(2+)](SR), SR Ca(2+) leak remains relatively constant during the declining phase of the Ca(2+) transient when [Ca(2+)](SR) and [Ca(2+)](i) change in opposite directions.
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