ArticleCirculation research2014
Junctional cleft [Ca²⁺]i measurements using novel cleft-targeted Ca²⁺ sensors.
Article in Circulation research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
38 citing papers in PubMed, 51 citations in OpenAlex.
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- Cardiac arrhythmogenesis: roles of ion channels and their functional modification.Frontiers in physiology · 2024Review
- Physiology of intracellular calcium buffering.Physiological reviews · 2023Review
- Feedback contributions to excitation-contraction coupling in native functioning striated muscle.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Probing spatiotemporal PKA activity at the ryanodine receptor and SERCA2a nanodomains in cardomyocytes.Cell communication and signaling : CCS · 2022Article
- Calcineurin in the heart: New horizons for an old friend.Cellular signalling · 2021Review
- Finite element analysis predicts CaScientific reports · 2021Article
- Detection of Ca2+ transients near ryanodine receptors by targeting fluorescent Ca2+ sensors to the triad.The Journal of general physiology · 2021Article
- Observing and Manipulating Cell-Specific Cardiac Function with Light.Advances in experimental medicine and biology · 2021Article
- Measurement of Myofilament-Localized Calcium Dynamics in Adult Cardiomyocytes and the Effect of Hypertrophic Cardiomyopathy Mutations.Circulation research · 2019Article
- Size Matters: Ryanodine Receptor Cluster Size Heterogeneity Potentiates Calcium Waves.Biophysical journal · 2019Article
- CaThe Biochemical journal · 2019Article
- Genetically Encoded Fluorescent Biosensors Illuminate the Spatiotemporal Regulation of Signaling Networks.Chemical reviews · 2018Review
- Hyperactive ryanodine receptors in human heart failure and ischaemic cardiomyopathy reside outside of couplons.Cardiovascular research · 2018Article
- Junctional membrane CaProceedings of the National Academy of Sciences of the United States of America · 2018Article
- Cardiac Arrhythmias as Manifestations of Nanopathies: An Emerging View.Frontiers in physiology · 2018Review
- Ambiguous interactions between diastolic and SR CaThe Journal of general physiology · 2017Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
rationaleIntracellular Ca(2+) concentration ([Ca(2+)]i) is regulated and signals differently in various subcellular microdomains, which greatly enhances its second messenger versatility. In the heart, sarcoplasmic reticulum Ca(2+) release and signaling are controlled by local [Ca(2+)]i in the junctional cleft ([Ca(2+)]Cleft), the small space between sarcolemma and junctional sarcoplasmic reticulum. However, methods to measure [Ca(2+)]Cleft directly are needed.
objectiveTo construct novel sensors that allow direct measurement of [Ca(2+)]Cleft. METHODS AND
resultsWe constructed cleft-targeted [Ca(2+)] sensors by fusing Ca(2+)-sensor GCaMP2.2 and a new lower Ca(2+)-affinity variant GCaMP2.2Low to FKBP12.6, which binds with high affinity and selectivity to ryanodine receptors. The fluorescence pattern, affinity for ryanodine receptors, and competition by untagged FKBP12.6 demonstrated that FKBP12.6-tagged sensors are positioned to measure local [Ca(2+)]Cleft in adult rat myocytes. Using GCaMP2.2Low-FKBP12.6, we showed that [Ca(2+)]Cleft reaches higher levels with faster kinetics than global [Ca(2+)]i during excitation-contraction coupling. Diastolic sarcoplasmic reticulum Ca(2+) leak or sarcolemmal Ca(2+) entry may raise local [Ca(2+)]Cleft above bulk cytosolic [Ca(2+)]i ([Ca(2+)]Bulk), an effect that may contribute to triggered arrhythmias and even transcriptional regulation. We measured this diastolic standing [Ca(2+)]Cleft-[Ca(2+)]Bulk gradient with GCaMP2.2-FKBP12.6 versus GCaMP2.2, using [Ca(2+)] measured without gradients as a reference point. This diastolic difference ([Ca(2+)]Cleft=194 nmol/L versus [Ca(2+)]Bulk=100 nmol/L) is dictated mainly by the sarcoplasmic reticulum Ca(2+) leak rather than sarcolemmal Ca(2+) flux.
conclusionsWe have developed junctional cleft-targeted sensors to measure [Ca(2+)]Cleft versus [Ca(2+)]Bulk and demonstrated dynamic differences during electric excitation and a standing diastolic [Ca(2+)]i gradient, which could influence local Ca(2+)-dependent signaling within the junctional cleft.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.