@article {42631,
	title = {Nanoscale organization of ryanodine receptor distribution and phosphorylation pattern determines the dynamics of calcium sparks},
	journal = {PLOS Computational Biology},
	volume = {18},
	year = {2022},
	month = {Jun-06-2022},
	pages = {e1010126},
	publisher = {PLOS},
	doi = {10.1371/journal.pcbi.1010126},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9203011/},
	author = {Mar{\'\i}a Hern{\'a}ndez {Mesa} and van den Brink, Jonas and William E. {Louch} and Kimberly J {McCabe} and Rangamani, Padmini},
	editor = {Jeffrey J. {Saucerman}}
}
@article {42622,
	title = {Prolonged β-adrenergic stimulation disperses ryanodine receptor clusters in cardiomyocytes},
	journal = {eLife},
	volume = {11},
	year = {2022},
	month = {Jan-08-2022},
	publisher = {eLife},
	address = {eLife},
	abstract = {Ryanodine Receptors (RyRs) exhibit dynamic arrangements in cardiomyocytes, and we previously showed that {\textquoteright}dispersion{\textquoteright} of RyR clusters disrupts Ca2+\&nbsp;homeostasis during heart failure (HF) (Kolstad\&nbsp;et al., eLife, 2018). Here, we investigated whether prolonged β-adrenergic stimulation, a hallmark of HF, promotes RyR cluster dispersion, and examined the underlying mechanisms. We observed that treatment of healthy rat cardiomyocytes with isoproterenol for 1 hour triggered progressive fragmentation of RyR clusters. Pharmacological inhibition of CaMKII reversed these effects, while cluster dispersion was reproduced by specific activation of CaMKII, and in mice with constitutively active Ser2814-RyR. A similar role of protein kinase A (PKA) in promoting RyR cluster fragmentation was established by employing PKA activation or inhibition. Progressive cluster dispersion was linked to declining Ca2+\&nbsp;spark fidelity and magnitude, and slowed release kinetics from Ca2+\&nbsp;propagation between more numerous RyR clusters. In healthy cells, this served to dampen the stimulatory actions of β-adrenergic stimulation over the longer term, and protect against pro-arrhythmic Ca2+\&nbsp;waves. However, during HF, RyR dispersion was linked to impaired Ca2+\&nbsp;release. Thus, RyR localization and function are intimately linked via channel phosphorylation by both CaMKII and PKA which, while finely tuned in healthy cardiomyocytes, underlies impaired cardiac function during pathology.ADD A COMMENT\&nbsp;+Open annotations. The current annotation count on this page is\&nbsp;0.Data availability},
	doi = {10.7554/eLife.77725},
	url = {https://elifesciences.org/articles/77725https://cdn.elifesciences.org/articles/77725/elife-77725-v1.pdfhttps://cdn.elifesciences.org/articles/77725/elife-77725-v1.xml},
	author = {Shen, Xin and van den Brink, Jonas and Bergan-Dahl, Anna and Terje R {Kolstad} and Einar Sjaastad {Norden} and Hou, Yufeng and Laasmaa, Martin and Aguilar-Sanchez, Yuriana and Ann Pepper {Quick} and Emil Knut Stene {Espe} and Sjaastad, Ivar and Xander HT {Wehrens} and Andrew G {Edwards} and Soeller, Christian and William Edward {Louch}}
}
@inbook {28434,
	title = {Calcium Signaling in Cardiomyocyte Models With Realistic Geometries},
	booktitle = {Zipes and Jalife{\textquoteright}s Cardiac Electrophysiology: From Cell to Bedside},
	volume = {1},
	year = {2021},
	month = {12/2021},
	pages = {362-375},
	publisher = { Elsevier},
	organization = { Elsevier},
	edition = {8},
	chapter = {32},
	author = {Andrew G {Edwards} and van den Brink, Jonas and Andrew D. {McCulloch}},
	editor = {Jalife, Jose and William G {Stevenson}}
}
@phdthesis {28433,
	title = {Computing Microscopic Structure-Function Relationships in Contraction of the Heart},
	volume = {PhD},
	year = {2021},
	month = {11/2021},
	pages = {162},
	type = {Collection of Articles},
	abstract = {The micro-anatomical structures within cardiac muscle\&nbsp;cells are specialized to produce force rapidly and reliably.\&nbsp;Especially important are nanoscopic domains in the cell\&nbsp;named dyads, which are crucial for coupling electrical excitation of the cell and its contraction. With disease, these dyads\&nbsp;become disrupted and broken down, leading to a weaker contraction. However, due to their incredibly small size, it has been hard to\&nbsp;quantify how structures change and how changed anatomical architecture\&nbsp;affects function. Computational modeling and analysis therefore plays a\&nbsp;critical role in furthering our understanding of structure-function relationships\&nbsp;in cardiac cells.In this work, we present new tools and techniques for imaging and analyzing\&nbsp;cardiac dyads using super-resolution microscopy. This allows for better\&nbsp;quantification of how dyads change with disease. Based on microscopy\&nbsp;data we also generate computational geometries which we combine\&nbsp;with mathematical reaction-diffusion\&nbsp; modeling to yield new insight into\&nbsp;structure-function relationships in contraction of the heart.},
	isbn = {15017710},
	author = {van den Brink, Jonas}
}
@misc {shen20203d,
	title = {3D Dstorm Imaging Reveals Camkii-Dependent Dispersal of Ryanodine Receptor Clusters in Failing Rat Cardiomyocytes},
	howpublished = {Biophysical Journal},
	year = {2020},
	publisher = {Cell Press},
	address = {Biophysical Journal},
	author = {Shen, Xin and Terje R {Kolstad} and van den Brink, Jonas and Frisk, Michael and Hou, Yufeng and Norden, Einar and Andrew G {Edwards} and Sjaastad, Ivar and Soeller, Christian and William E {Louch}}
}
@article {26347,
	title = {3D dSTORM imaging reveals novel detail of ryanodine receptor localization in rat cardiac myocytes},
	journal = {The Journal of Physiology},
	volume = {597},
	year = {2019},
	month = {Jan-15-2019},
	pages = {399-418},
	publisher = { Wiley-Blackwell},
	doi = {10.1113/jp277360},
	url = {https://physoc.onlinelibrary.wiley.com/doi/10.1113/JP277360},
	author = {Shen, Xin and van den Brink, Jonas and Hou, Yufeng and Colli, Dylan and Le, Christopher and Terje R. {Kolstad} and MacQuaide, Niall and Cathrine R. {Carlson} and Peter M. {Kekenes-Huskey} and Andrew G {Edwards} and Soeller, Christian and William E. {Louch}}
}
@article {26194,
	title = {A Kirchhoff-Nernst-Planck framework for modeling large scale extracellular electrodiffusion surrounding morphologically detailed neurons},
	journal = {PLOS Computational Biology},
	volume = {14},
	number = {1-26},
	year = {2018},
	month = {10/2018},
	publisher = {Public Library of Science},
	abstract = {Many pathological conditions, such as seizures, stroke, and spreading depression, are associated with substantial changes in ion concentrations in the extracellular space (ECS) of the brain. An understanding of the mechanisms that govern ECS concentration dynamics may be a prerequisite for understanding such pathologies. To estimate the transport of ions due to electrodiffusive effects, one must keep track of both the ion concentrations and the electric potential simultaneously in the relevant regions of the brain. Although this is currently unfeasible experimentally, it is in principle achievable with computational models based on biophysical principles and constraints. Previous computational models of extracellular ion-concentration dynamics have required extensive computing power, and therefore have been limited to either phenomena on very small spatiotemporal scales (micrometers and milliseconds), or simplified and idealized 1-dimensional (1-D) transport processes on a larger scale. Here, we present the 3-D Kirchhoff-Nernst-Planck (KNP) framework, tailored to explore electrodiffusive effects on large spatiotemporal scales. By assuming electroneutrality, the KNP-framework circumvents charge-relaxation processes on the spatiotemporal scales of nanometers and nanoseconds, and makes it feasible to run simulations on the spatiotemporal scales of millimeters and seconds on a standard desktop computer. In the present work, we use the 3-D KNP framework to simulate the dynamics of ion concentrations and the electrical potential surrounding a morphologically detailed pyramidal cell. In addition to elucidating the single neuron contribution to electrodiffusive effects in the ECS, the simulation demonstrates the efficiency of the 3-D KNP framework. We envision that future applications of the framework to more complex and biologically realistic systems will be useful in exploring pathological conditions associated with large concentration variations in the ECS.},
	doi = {10.1371/journal.pcbi.1006510},
	url = {http://dx.plos.org/10.1371/journal.pcbi.1006510},
	author = {Solbr{\r a}, Andreas and Bergersen, Aslak and van den Brink, Jonas and Malthe-S{\o}renssen, Anders and Gaute T. {Einevoll} and Halnes, Geir},
	editor = {Barreto, Ernest}
}
@article {26326,
	title = {Ryanodine Receptor Dispersion Disrupts Ca2+-Release in Failing Cardiac Myocytes},
	journal = {eLife},
	volume = {7},
	year = {2018},
	month = {10/2018},
	pages = {e39427},
	publisher = {eLife Sciences Publications},
	issn = {2050-084X},
	doi = {10.7554/eLife.39427},
	url = {https://elifesciences.org/articles/39427},
	author = {Terje R {Kolstad} and van den Brink, Jonas and MacQuaide, Niall and Per Kristian {Lunde} and Frisk, Michael and Jan Magnus {Aronsen} and Einar S {Norden} and Cataliotti, Alessandro and Sjaastad, Ivar and Ole M {Sejersted} and Andrew G {Edwards} and Glenn T. {Lines} and William E {Louch}}
}
@article {skibsbye2016refractoriness,
	title = {Refractoriness in human atria: time and voltage dependence of sodium channel availability},
	journal = {Journal of molecular and cellular cardiology},
	volume = {101},
	year = {2016},
	pages = {26{\textendash}34},
	publisher = {{Academic Press},
	author = {Skibsbye, Lasse and Jespersen, Thomas and Christ, Torsten and Maleckar, Molly and van den Brink, Jonas and Tavi, Pasi and Jussi T {Koivum{\"a}ki}}
}
@article {25026,
	title = {Refractoriness in human atria: Time and voltage dependence of sodium channel availability},
	journal = {Journal of Molecular and Cellular Cardiology},
	volume = {101},
	year = {2016},
	month = {12/2016},
	pages = {26-34},
	publisher = {Elsevier},
	doi = {10.1016/j.yjmcc.2016.10.009},
	url = {https://doi.org/10.1016/j.yjmcc.2016.10.009},
	author = {Skibsbye, Lasse and Jespersen, Thomas and Maleckar, Molly and van den Brink, Jonas and Tavi, Pasi and Koivum{\"a}ki, Jussi}
}
