scholarly journals Calcium Regulation of Single Ryanodine Receptor Channel Gating Analyzed Using HMM/MCMC Statistical Methods

2004 ◽  
Vol 123 (5) ◽  
pp. 533-553 ◽  
Author(s):  
Rafael A. Rosales ◽  
Michael Fill ◽  
Ariel L. Escobar

Type-II ryanodine receptor channels (RYRs) play a fundamental role in intracellular Ca2+ dynamics in heart. The processes of activation, inactivation, and regulation of these channels have been the subject of intensive research and the focus of recent debates. Typically, approaches to understand these processes involve statistical analysis of single RYRs, involving signal restoration, model estimation, and selection. These tasks are usually performed by following rather phenomenological criteria that turn models into self-fulfilling prophecies. Here, a thorough statistical treatment is applied by modeling single RYRs using aggregated hidden Markov models. Inferences are made using Bayesian statistics and stochastic search methods known as Markov chain Monte Carlo. These methods allow extension of the temporal resolution of the analysis far beyond the limits of previous approaches and provide a direct measure of the uncertainties associated with every estimation step, together with a direct assessment of why and where a particular model fails. Analyses of single RYRs at several Ca2+ concentrations are made by considering 16 models, some of them previously reported in the literature. Results clearly show that single RYRs have Ca2+-dependent gating modes. Moreover, our results demonstrate that single RYRs responding to a sudden change in Ca2+ display adaptation kinetics. Interestingly, best ranked models predict microscopic reversibility when monovalent cations are used as the main permeating species. Finally, the extended bandwidth revealed the existence of novel fast buzz-mode at low Ca2+ concentrations.

1990 ◽  
Vol 58 (2) ◽  
pp. 471-481 ◽  
Author(s):  
H.H. Valdivia ◽  
C. Valdivia ◽  
J. Ma ◽  
R. Coronado

2003 ◽  
Vol 376 (3) ◽  
pp. 807-812 ◽  
Author(s):  
Gábor BÁNHEGYI ◽  
Miklós CSALA ◽  
Gábor NAGY ◽  
Vincenzo SORRENTINO ◽  
Rosella FULCERI ◽  
...  

In the present study, we have investigated the role of RyR1 (ryanodine receptor calcium channel type 1) in glutathione (GSH) transport through the sarcoplasmic reticulum (SR) membrane of skeletal muscles. Lanthanum chloride, a prototypic blocker of cation channels, inhibited the influx and efflux of GSH in SR vesicles. Using a rapid-filtration-based assay and lanthanum chloride as a transport blocker, an uptake of radiolabelled GSH into SR vesicles was observed. Pretreatment of SR vesicles with the RyR1 antagonists Ruthenium Red and ryanodine as well as with lanthanum chloride blocked the GSH uptake. An SR-like GSH uptake appeared in microsomes obtained from an HEK-293 (human embryonic kidney 293) cell line after transfection of RyR1. These observations strongly suggest that RyR1 mediates GSH transport through the SR membranes of skeletal muscles.


2016 ◽  
Vol 291 (50) ◽  
pp. 26024-26034 ◽  
Author(s):  
Bo Sun ◽  
Wenting Guo ◽  
Xixi Tian ◽  
Jinjing Yao ◽  
Lin Zhang ◽  
...  

2007 ◽  
Vol 24 (3) ◽  
pp. 185-193 ◽  
Author(s):  
Kishani M. Ranatunga ◽  
S. R. Wayne Chen ◽  
Luc Ruest ◽  
William Welch ◽  
Alan J. Williams

2004 ◽  
Vol 87 (4) ◽  
pp. 2335-2351 ◽  
Author(s):  
William Welch ◽  
Shana Rheault ◽  
Duncan J. West ◽  
Alan J. Williams

1991 ◽  
Vol 13 (5) ◽  
pp. 231-234 ◽  
Author(s):  
Helge Erik Solberg ◽  
D. Stamm

This paper is the fourth in a series of Recommendations on the Theory of Reference Values. The others cover:Part 1. The Concept of Reference Values [1].Part 2. Selection of Individuals for the Production of Reference Values [2].Part 3. Preparation of Individuals and Collection of Specimens for the Production of Reference Values [3].Part 5. Statistical Treatment of Collected Reference Values. Determination of Reference Limits [4].Part 6. Presentation of Observed Values Related to Reference Values [5].A Guide to the Documents is currently in preparation.The Expert Panel of Theory of Reference Values (EPTRV) was created in 1970 by the Committee on Standards (at present: Scientific Division) of the International Federation of Clinical Chemistry (IFCC). Its task was to develop a nomenclature and recommend procedures for the production of reference values and their treatment, and presentation of observed values in relation to reference data.The first document in the above-mentioned series describes the subject of reference values and defines various terms. It would be best to read it for a thorough understanding of the present document.


A mathematical analysis of the factors affecting the distribution of oxygen in living tissue is the subject of this paper. The Erlang -Krogh equation discussed in § 1 is derived from a highly simplified model, comprising a long, straight capillary surrounded by a cylinder of respiring tissue. Succeeding sections describe the effects upon the distribution of oxygen as predicted by this model of the following factors: ( a ) Hexagonal rather than cylindrical symmetry. ( b ) Decrease in the rate of consumption of oxygen by the cells in the tissue when the oxygen tension falls below a certain value. ( c ) Variation of the diffusion constant with position in the tissue. ( d ) A sudden change in the value of the oxygen tension at the capillary surface. ( e ) A decrease in oxygen tension along the length of the capillary. ( f ) Fluid flow in the extracellular fluid.


2019 ◽  
Author(s):  
Ximin Chi ◽  
Deshun Gong ◽  
Kang Ren ◽  
Gewei Zhou ◽  
Gaoxingyu Huang ◽  
...  

AbstractThe type-2 ryanodine receptor (RyR2) is responsible for releasing Ca2+ from the sarcoplasmic reticulum of cardiomyocytes, subsequently leading to muscle contraction. Here, we report four cryo-EM structures of porcine RyR2 bound to distinct modulators that collectively provide mechanistic insight into RyR2 regulation. Ca2+ alone induces a contraction of the Central domain that facilitates the dilation of S6 bundle, but is insufficient to open the pore. The small molecule agonist PCB95 helps Ca2+ to overcome the barrier for opening. FKBP12.6 induces a relaxation of the Central domain that decouples it from the S6 bundle, stabilizing RyR2 in a closed state. Caffeine locks the Central domain in a constitutively contracted state, while further addition of ATP opens the channel by strengthening the coupling between the U-motif and S6. Our study marks an important step towards mechanistic understanding of the complicated regulation of this key channel whose aberrant activity engenders life-threatening cardiac disorders.


2019 ◽  
Vol 116 (3) ◽  
pp. 521a-522a
Author(s):  
Toshiko Yamazawa ◽  
Haruo Ogawa ◽  
Maki Yamaguchi ◽  
Takashi Murayama ◽  
Hideto Oyamada ◽  
...  

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