@article{Zima_2008_105, abstract = {Ca(2+) release from cardiac sarcoplasmic reticulum (SR) via ryanodine receptors (RyRs) is regulated by dyadic cleft [Ca(2+)] and intra-SR free [Ca(2+)] ([Ca(2+)](SR)). Robust SR Ca(2+) release termination is important for stable excitation-contraction coupling, and partial [Ca(2+)](SR) depletion may contribute to release termination. Here, we investigated the regulation of SR Ca(2+) release termination of spontaneous local SR Ca(2+) release events (Ca(2+) sparks) by [Ca(2+)](SR), release flux, and intra-SR Ca(2+) diffusion. We simultaneously measured Ca(2+) sparks and Ca(2+) blinks (localized elementary [Ca(2+)](SR) depletions) in permeabilized ventricular cardiomyocytes over a wide range of SR Ca(2+) loads and release fluxes. Sparks terminated via a [Ca(2+)](SR)-dependent mechanism at a fixed [Ca(2+)](SR) depletion threshold independent of the initial [Ca(2+)](SR) and release flux. Ca(2+) blink recovery depended mainly on intra-SR Ca(2+) diffusion rather than SR Ca(2+) uptake. Therefore, the large variation in Ca(2+) blink recovery rates at different release sites occurred because of differences in the degree of release site interconnection within the SR network. When SR release flux was greatly reduced, long-lasting release events occurred from well-connected junctions. These junctions could sustain release because local SR Ca(2+) release and [Ca(2+)](SR) refilling reached a balance, preventing [Ca(2+)](SR) from depleting to the termination threshold. Prolonged release events eventually terminated at a steady [Ca(2+)](SR), indicative of a slower, [Ca(2+)](SR)-independent termination mechanism. These results demonstrate that there is high variability in local SR connectivity but that SR Ca(2+) release terminates at a fixed [Ca(2+)](SR) termination threshold. Thus, reliable SR Ca(2+) release termination depends on tight RyR regulation by [Ca(2+)](SR).}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Zima, Aleksey V and Picht, Eckard and Bers, Donald M and Blatter, Lothar A}, biburl = {https://www.bibsonomy.org/bibtex/23665daf6805d4b4504be66c0f6a0774a/hake}, description = {The whole bibliography file I use.}, doi = {10.1161/CIRCRESAHA.107.183236}, file = {Zima_2008_105.pdf:Zima_2008_105.pdf:PDF}, institution = {Department of Molecular Biophysics and Physiology, Rush University Medical Center, Chicago, IL 60612, USA.}, interhash = {a5117492f11275c292efde03676ad31a}, intrahash = {3665daf6805d4b4504be66c0f6a0774a}, journal = {Circ Res}, keywords = {ATPases, Animals; Blockers, Calcium Calcium-Transporting Cardiac, Channel Channel, Diffusion; Fluorescence; Heart Kinetics; Membrane Microscopy, Myocytes, Permeability; Potentials; Rabbits; Receptor Release Reticulum Reticulum, Ryanodine Sarcoplasmic Signaling, Ventricles, drug effects/enzymology/metabolism effects/enzymology/metabolism; effects/metabolism; effects; metabolism; pharmacology;}, month = Oct, number = 8, pages = {e105--e115}, pdf = {Zima_2008_105.pdf}, pii = {CIRCRESAHA.107.183236}, pmid = {18787194}, timestamp = {2009-06-03T11:21:39.000+0200}, title = {Termination of cardiac Ca2+ sparks: role of intra-SR [Ca2+], release flux, and intra-SR Ca2+ diffusion.}, url = {http://dx.doi.org/10.1161/CIRCRESAHA.107.183236}, volume = 103, year = 2008 } @article{Zhao_2001_13810, abstract = {As an inhibitor of {C}a$^{2+}$ release through ryanodine receptor (RYR) channels, the skeletal muscle relaxant dantrolene has proven to be both a valuable experimental probe of intracellular {C}a$^{2+}$ signaling and a lifesaving treatment for the pharmacogenetic disorder malignant hyperthermia. However, the molecular basis and specificity of the actions of dantrolene on RYR channels have remained in question. Here we utilize [(3)H]ryanodine binding to further investigate the actions of dantrolene on the three mammalian RYR isoforms. The inhibition of the pig skeletal muscle RYR1 by dantrolene (10 microm) was associated with a 3-fold increase in the K(d) of [(3)H]ryanodine binding to sarcoplasmic reticulum (SR) vesicles such that dantrolene effectively reversed the 3-fold decrease in the K(d) for [(3)H]ryanodine binding resulting from the malignant hyperthermia RYR1 Arg(615) --> Cys mutation. Dantrolene inhibition of the RYR1 was dependent on the presence of the adenine nucleotide and calmodulin and reflected a selective decrease in the apparent affinity of RYR1 activation sites for {C}a$^{2+}$ relative to {M}g$^{2+}$. In contrast to the RYR1 isoform, the cardiac RYR2 isoform was unaffected by dantrolene, both in native cardiac SR vesicles and when heterologously expressed in HEK-293 cells. By comparison, the RYR3 isoform expressed in HEK-293 cells was significantly inhibited by dantrolene, and the extent of RYR3 inhibition was similar to that displayed by the RYR1 in native SR vesicles. Our results thus indicate that both the RYR1 and the RYR3, but not the RYR2, may be targets for dantrolene inhibition in vivo.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Zhao, F. and Li, P. and Chen, S. R. and Louis, C. F. and Fruen, B. R.}, biburl = {https://www.bibsonomy.org/bibtex/2a709303295845de834cceb11950272ae/hake}, description = {The whole bibliography file I use.}, doi = {10.1074/jbc.M006104200}, interhash = {3fd4fcb34797accb005eef4fa23a44ef}, intrahash = {a709303295845de834cceb11950272ae}, journal = {J. Biol. Chem.}, keywords = {11278295 50, Acid, Adenine, Adenosine Alanine, Animals, Arginine, Binding Binding, Caffeine, Calcium Calcium, Cell Central Central, Channel Channel, Chloride, Cloning, Co, Complementary, Concentration Conformation, Cryoelectron Cysteine, DNA, Dantrolene, Dominant, Dose-Response Drug, Electrophysiology, Fusion Gating, Genes, Gl, Glutamic Glutathione Gov't, Heart, Humans, Inhibitory Ion Isoforms, Kinetics, Line, Magnesium Magnesium, Mice, Microscopy, Molecular, Muscle Muscle, Mutation, Myocardium, Nervous Non-U.S. P.H.S., Point Protein Proteins, Receptor Recombinant Relationship, Relaxants, Release Research Reticulum, Ryanodine Ryanodine, Sarcoplasmic Signal Sites, Skeletal, Stimulants, Strontium, Support, Swine, System Transduction, Transfection, Transferase, Triphosphate, U.S. ntraction, utamic}, month = Apr, number = 17, pages = {13810--13816}, pii = {M006104200}, pmid = {11278295}, timestamp = {2009-06-03T11:21:39.000+0200}, title = {Dantrolene inhibition of ryanodine receptor {C}a$^{2+}$ release channels. Molecular mechanism and isoform selectivity.}, url = {http://dx.doi.org/10.1074/jbc.M006104200}, volume = 276, year = 2001 } @article{Zahr_1999_787, abstract = {The local control concept of excitation-contraction coupling in the heart postulates that the activity of the sarcoplasmic reticulum ryanodine receptor channels (RyR) is controlled by {C}a$^{2+}$ entry through adjoining sarcolemmal single dihydropyridine receptor channels (DHPRs). One unverified premise of this hypothesis is that the RyR must be fast enough to track the brief (<0.5 ms) {C}a$^{2+}$ elevations accompanying single DHPR channel openings. To define the kinetic limits of effective trigger {C}a$^{2+}$ signals, we recorded activity of single cardiac RyRs in lipid bilayers during rapid and transient increases in {C}a$^{2+}$ generated by flash photolysis of DM-nitrophen. Application of such {C}a$^{2+}$ spikes (amplitude approximately 10-30 microM, duration approximately 0.1-0.4 ms) resulted in activation of the RyRs with a probability that increased steeply (apparent Hill slope approximately 2.5) with spike amplitude. The time constants of RyR activation were 0.07-0.27 ms, decreasing with spike amplitude. To fit the rising portion of the open probability, a single exponential function had to be raised to a power n approximately 3. We show that these data could be adequately described with a gating scheme incorporating four sequential {C}a$^{2+}$-sensitive closed states between the resting and the first open states. These results provide evidence that brief {C}a$^{2+}$ triggers are adequate to activate the RyR, and support the possibility that RyR channels are governed by single DHPR openings. They also provide evidence for the assumption that RyR activation requires binding of multiple {C}a$^{2+}$ ions in accordance with the tetrameric organization of the channel protein.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Zahradn�kov�, A. and Zahradn�k, I. and Gy�rke, I. and Gy�rke, S.}, biburl = {https://www.bibsonomy.org/bibtex/2083b767445fca91eef813d8063b4fe6b/hake}, description = {The whole bibliography file I use.}, file = {Zahr_1999_787.pdf:Zahr_1999_787.pdf:PDF}, interhash = {199300d783506b45309aca59e6550553}, intrahash = {083b767445fca91eef813d8063b4fe6b}, journal = {J. Gen. Physiol.}, keywords = {10578015 Acetic Acids, Agents, Algorithms, Animals, Bilayers, Biological, Calcium Calcium, Cardiac, Cells, Channel Channel, Chelating Cultured, Dogs, Dose-Response Drug, Ethylenediamines, Gating, Gov't, Heart, In Ion Kinetics, Lipid Magnesium, Microsomes, Models, Myocardium, Myocytes, Non-U.S. P.H.S., Patch-Clamp Photolysis, Receptor Relationship, Release Research Reticulum, Ryanodine Sarcoplasmic Signaling, Support, Techniques, U.S. Vitro,}, month = Dec, number = 6, pages = {787--798}, pdf = {Zahr_1999_787.pdf}, pmid = {10578015}, timestamp = {2009-06-03T11:21:38.000+0200}, title = {Rapid activation of the cardiac ryanodine receptor by submillisecond calcium stimuli.}, url = {http://www.jgp.org/cgi/content/full/114/6/787}, volume = 114, year = 1999 } @article{Zahr_1995_1780, abstract = {Single channel activity of the cardiac ryanodine-sensitive calcium-release channel in planar lipid membranes was studied in order to elucidate the calcium-dependent mechanism of its steady-state behavior. The single channel kinetics, observed with Cs+ as the charge carrier at different activating (cis) {C}a$^{2+}$ concentrations in the absence of ATP and Mg2+, were similar to earlier reports and were extended by analysis of channel modal behavior. The channel displayed three episodic levels of open probability defining three gating modes: H (high activity), L (low activity), and I (no activity). The large difference in open probabilities between the two active modes resulted from different bursting patterns and different proportions of two distinct channel open states. I-mode was without openings and can be regarded as the inactivated mode of the channel; L-mode was composed of short and sparse openings; and H-mode openings were longer and grouped into bursts. Modal gating may explain calcium-release channel adaptation (as transient prevalence of H-mode after {C}a$^{2+}$ binding) and the inhibitory effects of drugs (as stabilization of mode I), and it provides a basis for understanding the regulation of calcium release.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Zahradn�kov�, A. and Zahradn�k, I.}, biburl = {https://www.bibsonomy.org/bibtex/25a2bb00233c8e5016b03d468fe666180/hake}, description = {The whole bibliography file I use.}, file = {Zahr_1995_1780.pdf:Zahr_1995_1780.pdf:PDF}, interhash = {bfb230365a19ceae92236693393f57c1}, intrahash = {5a2bb00233c8e5016b03d468fe666180}, journal = {Biophys. J.}, keywords = {8580321 Adaptation, Animals, Biophysics, Calcium Calcium, Cations, Chains, Channel Channel, Channels, Comparative Computer Divalent, Dogs, Endoplasmic Factors, Gating, Gov't, Heart, In Ion Kinetics, Lipids, Markov Membrane Models, Monovalent, Muscle Myocardium, Non-U.S. Physiological, Probability, Proteins, Receptor Release Research Reticulum, Ryanodine Simulation, Study, Support, Theoret, Time Vitro, ical,}, month = Nov, number = 5, pages = {1780--1788}, pmid = {8580321}, timestamp = {2009-06-03T11:21:38.000+0200}, title = {Description of modal gating of the cardiac calcium release channel in planar lipid membranes.}, url = {http://www.pubmedcentral.gov/articlerender.fcgi?tool=pubmed&pubmedid=8580321}, volume = 69, year = 1995 } @article{Zahr_1996_2996, abstract = {A Markovian model of the cardiac Ca release channel, based on experimental single-channel gating data, was constructed to understand the transient nature of Ca release. The rate constants for a minimal gating scheme with one Ca-free resting state, and with two open and three closed states with one bound {C}a$^{2+}$, were optimized to simulate the following experimental findings. In steady state the channel displays three modes of activity: inactivated 1 mode without openings, low-activity L mode with single openings, and high-activity H mode with bursts of openings. At the onset of a {C}a$^{2+}$ step, the channel first activates in H mode and then slowly relaxes to a mixture of all three modes, the distribution of which depends on the new {C}a$^{2+}$. The corresponding ensemble current shows rapid activation, which is followed by a slow partial inactivation. The transient reactivation of the channel (increment detection) in response to successive additions of {C}a$^{2+}$ is then explained by the model as a gradual recruitment of channels from the extant pool of channels in the resting state. For channels in a living cell, the model predicts a high level of peak activation, a high extent of inactivation, and rapid deactivation, which could underlie the observed characteristics of the elementary release events (calcium sparks).}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Zahradn�kov�, A. and Zahradn�k, I.}, biburl = {https://www.bibsonomy.org/bibtex/2707fbfbccbd9eaebbe0d8fd148388fd0/hake}, description = {The whole bibliography file I use.}, file = {Zahr_1996_2996.pdf:Zahr_1996_2996.pdf:PDF}, interhash = {c5bc293454cac888decc19bb52bc1794}, intrahash = {707fbfbccbd9eaebbe0d8fd148388fd0}, journal = {Biophys. J.}, keywords = {8968571 Animals, Calcium Calcium, Cations, Chains, Channel Channel, Channels, Comparative Computer Divalent, Endoplasmic Factors, Gating, Gov't, Heart, Ion Kinetics, Markov Models, Monovalent, Myocardium, Non-U.S. Probability, Receptor Release Research Reticulum, Ryanodine Simulation, Study, Support, Theoret, Time ical,}, month = Dec, number = 6, pages = {2996--3012}, pmid = {8968571}, timestamp = {2009-06-03T11:21:38.000+0200}, title = {A minimal gating model for the cardiac calcium release channel.}, url = {http://www.pubmedcentral.gov/articlerender.fcgi?tool=pubmed&pubmedid=8968571}, volume = 71, year = 1996 } @article{Zahr_1999_268, abstract = {The planar lipid bilayer and vesicle release experiments are two alternative approaches used to study the function of the ryanodine receptor (RyR) channel at the subcellular level. In this work, we combine models of gating (Zahradn�kov� and Zahradn�k, Biophys. J. 71 (1996) 2996-3012) and permeation (Tinker et al., J. Gen. Physiol. 100 (1992) 495-517) of the cardiac RyR channel to simulate calcium release experiments on sarcoplasmic reticulum vesicles. The resulting model and real experimental data agreed well within the experimental scatter, confirming indistinguishable properties of the Ry{RC} in the vesicle preparation and in the planar lipid bilayer. The previously observed differences in calcium dependencies of the release and the gating processes can be explained by binding of calcium within the Ry{RC} conducting pore. A novel method of analysis of calcium dependence of calcium release was developed and tested. Three gating models of the Ry{RC}, showing, respectively, an increase, no change, and a decrease in calcium sensitivity over time, were compared. The described method of analysis enabled determination of temporal changes in calcium sensitivity, giving potential for detection of the adaptation/inactivation phenomena of the Ry{RC} in both vesicle and in situ release experiments.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Zahradn�kov�, A. and Zahradn�k, I.}, biburl = {https://www.bibsonomy.org/bibtex/2bfb7ec6dd00fea8a57bb68708b447808/hake}, description = {The whole bibliography file I use.}, file = {Zahr_1999_268.pdf:Zahr_1999_268.pdf:PDF}, interhash = {446a40bc7f497ef369fa6a44f835bc1a}, intrahash = {bfb7ec6dd00fea8a57bb68708b447808}, journal = {Biochim. Biophys. Acta}, key = 218, keywords = {10320679 Calcium Calcium, Cations, Channel Channel, Computer Divalent, Endoplasmic Gating, Gov't, Ion Kinetics, Monovalent, Myocardium, Non-U.S. Receptor Release Research Reticulum, Ryanodine Simulation, Support,}, month = May, number = 2, pages = {268--284}, pmid = {10320679}, timestamp = {2009-06-03T11:21:38.000+0200}, title = {Analysis of calcium-induced calcium release in cardiac sarcoplasmic reticulum vesicles using models derived from single-channel data.}, url = {http://dx.doi.org/10.1016/S0005-2736(99)00036-X}, volume = 1418, year = 1999 } @article{Zahr_2007_677, abstract = {The local calcium release flux signals (calcium spikes) evoked by membrane depolarization were recorded at high temporal resolution (2000 lines s(-1)) in isolated ventricular myocytes of male rats, using combination of scanning confocal microscopy and the patch-clamp technique. The kinetic properties of calcium spikes were investigated. The time course of calcium spike activation could be described reliably by a model with higher-order (n = 3) kinetics, but not by a first-order exponential process. A model of calcium spike with calcium release termination coupled to its activation was preferential to a model with the release termination independent of its activation. Three fluorescent calcium dyes (OG-5N, fluo-3, and fluo-4) were compared for calcium spike measurements. Experimental measurements as well as simulations showed that the occurrence and latency of calcium spikes could be measured faithfully with all indicators, while the kinetics of calcium spikes was reliably traced only with OG-5N. Calcium spikes evoked by a step depolarization from -50 to 0 mV commenced with a mean latency of 4.1 +/- 0.2 ms and peaked 6.7 +/- 0.2 ms later. Their full amplitudes were normally distributed. The activation time constant of calcium spikes was 3.1 +/- 0.1 ms, and the time constant of termination was 5.5 +/- 0.2 ms. A negative correlation was observed between the observed amplitude of calcium spikes and their time constant of activation, but there was no correlation between their observed amplitude and time constant of termination, in agreement with the concept of steep calcium-dependent activation and fateful inactivation of calcium release flux.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Zahradn�kov�, Alexandra and Pol�kov�, Eva and Zahradn�k, Ivan and Zahradn�kov�, Alexandra}, biburl = {https://www.bibsonomy.org/bibtex/258e9b907ecdc74367a033b792591e914/hake}, description = {The whole bibliography file I use.}, doi = {10.1113/jphysiol.2006.117796}, file = {Zahr_2007_677.pdf:Zahr_2007_677.pdf:PDF;Zahr_2007_677.pdf:Zahr_2007_677.pdf:PDF}, institution = {ra.zahradnikova@savba.sk}, interhash = {dc49a412cb4592efa8a598ce6d6a7179}, intrahash = {58e9b907ecdc74367a033b792591e914}, journal = {J. Physiol.}, keywords = {Animals; Cal; Calcium Calcium; Cardiac; Channel; Dyes; Factors; Fluorescent Male; Membrane Models, Myocytes, Potentials; Rats, Rats; Receptor Release Ryanodine Signaling Theoretical; Time Wistar; cium}, month = Feb, number = {Pt 3}, pages = {677--691}, pii = {jphysiol.2006.117796}, pmid = {17124272}, timestamp = {2009-06-03T11:21:38.000+0200}, title = {Kinetics of calcium spikes in rat cardiac myocytes.}, url = {http://dx.doi.org/10.1113/jphysiol.2006.117796}, volume = 578, year = 2007 } @article{Zahr_2004_C330, abstract = {In mammalian cardiac myocytes, calcium released into the dyadic space rapidly inactivates calcium current (ICa). We used this {C}a$^{2+}$ release-dependent inactivation (RDI) of ICa as a local probe of sarcoplasmic reticulum {C}a$^{2+}$ release activation. In whole cell patch-clamped rat ventricular myocytes, {C}a$^{2+}$ entry induced by short prepulses from -50 mV to positive voltages caused suppression of peak ICa during a test pulse. The negative correlation between peak ICa suppression and ICa inactivation during the test pulse indicated that RDI evoked by the prepulse affected only calcium channels in those dyads in which calcium release was activated. {C}a$^{2+}$ ions injected during the prepulse and during the subsequent tail current suppressed peak ICa in the test pulse to a different extent. Quantitative analysis indicated that equal {C}a$^{2+}$ charge was 3.5 times less effective in inducing release when entering during the prepulse than when entering during the tail. Tail {C}a$^{2+}$ charge injected by the first voltage-dependent calcium channel (DHPR) openings was three times less effective than that injected by DHPR reopenings. These findings suggest that calcium release activation can be profoundly influenced by the recent history of L-type {C}a$^{2+}$ channel activity due to potentiation of ryanodine receptors (RyRs) by previous calcium influx. This conclusion was confirmed at the level of single RyRs in planar lipid bilayers: using flash photolysis of the calcium cage NP-EGTA to generate two sequential calcium stimuli, we showed that RyR activation in response to the second stimulus was four times higher than that in response to the first stimulus.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Zahradn�kov�, Alexandra and Kubalov�, Zuzana and Pavelkov�, Jana and Gy�rke, S�ndor and Zahradn�k, Ivan}, biburl = {https://www.bibsonomy.org/bibtex/2d24441278a5e83a24e33b8f8255c7135/hake}, description = {The whole bibliography file I use.}, doi = {10.1152/ajpcell.00272.2003}, file = {Zahr_2004_C330.pdf:Zahr_2004_C330.pdf:PDF}, interhash = {49b8471595ae260cd90b62446d7fceef}, intrahash = {d24441278a5e83a24e33b8f8255c7135}, journal = {Am. J. Physiol. Cell Physiol.}, keywords = {14522820 Animals, Calcium Calcium, Cardiac, Cardiovascular, Channel, Channels, Conductivity, Electric Gov't, Male, Models, Myocytes, Non-U.S. P.H.S., Patch-Clamp Rats, Receptor Release Research Ryanodine Stimulation, Support, Techniques, U.S. Wistar,}, month = Feb, number = 2, pages = {C330--C341}, pii = {00272.2003}, pmid = {14522820}, timestamp = {2009-06-03T11:21:38.000+0200}, title = {Activation of calcium release assessed by calcium release-induced inactivation of calcium current in rat cardiac myocytes.}, url = {http://dx.doi.org/10.1152/ajpcell.00272.2003}, volume = 286, year = 2004 } @article{Zahr_2003_C1059, abstract = {Mg2+, an important constituent of the intracellular milieu in cardiac myocytes, is known to inhibit ryanodine receptor (RyR) {C}a$^{2+}$ release channels by competing with {C}a$^{2+}$ at the cytosolic activation sites of the channel. However, the significance of this competition for local, dynamic {C}a$^{2+}$-signaling processes thought to govern cardiac excitation-contraction (EC) coupling remains largely unknown. In the present study, {C}a$^{2+}$ stimuli of different waveforms (i.e., sustained and brief) were generated by photolysis of the caged {C}a$^{2+}$ compound nitrophenyl (NP)-EGTA. The evoked RyR activity was measured in planar lipid bilayers in the presence of 0.6-1.3 mM free Mg2+ at the background of 3 mM total ATP in the presence or absence of 1 mM luminal {C}a$^{2+}$. Mg2+ dramatically slowed the rate of activation of RyRs in response to sustained (> or =10-ms) elevations in {C}a$^{2+}$ concentration. Paradoxically, Mg2+ had no measurable impact on the kinetics of the RyR response induced by physiologically relevant, brief (<1-ms) {C}a$^{2+}$ stimuli. Instead, the changes in activation rate observed with sustained stimuli were translated into a drastic reduction in the probability of responses. Luminal {C}a$^{2+}$ did not affect the peak open probability or the probability of responses to brief {C}a$^{2+}$ signals; however, it slowed the transition to steady state and increased the steady-state open probability of the channel. Our results indicate that Mg2+ is a critical physiological determinant of the dynamic behavior of the RyR channel, which is expected to profoundly influence the fidelity of coupling between L-type {C}a$^{2+}$ channels and RyRs in heart cells.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Zahradn�kov�, A. and Dura, M. and Gy�rke, I. and Escobar, A. L. and Zahradn�k, I. and Gy�rke, S.}, biburl = {https://www.bibsonomy.org/bibtex/25626b6a3b6ca2ac617f9a5ca86a3b076/hake}, description = {The whole bibliography file I use.}, doi = {10.1152/ajpcell.00118.2003}, file = {Zahr_2003_C1059.pdf:Zahr_2003_C1059.pdf:PDF}, institution = {Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Vl�rska 5, 833 34 Bratislava, Slovak Republic. alexandra.zahradnikova@savba.sk}, interhash = {f8889acf97c576ac5a2b058b501943b7}, intrahash = {5626b6a3b6ca2ac617f9a5ca86a3b076}, journal = {Am. J. Physiol. Cell Physiol.}, keywords = {Animals; Calcium Calcium; Cardiac; Cells, Channel Cultured; Dogs; Dose-Response Drug; Magnesium; Myocytes, Receptor Relationship, Release Ryanodine}, month = Nov, number = 5, pages = {C1059--C1070}, pdf = {Zahr_2003_C1059.pdf}, pii = {00118.2003}, pmid = {12839831}, timestamp = {2009-06-03T11:21:38.000+0200}, title = {Regulation of dynamic behavior of cardiac ryanodine receptor by Mg2+ under simulated physiological conditions.}, url = {http://ajpcell.physiology.org/cgi/content/full/285/5/C1059}, volume = 285, year = 2003 } @article{Yano_2005_556, abstract = {Structural and functional alterations in the {C}a$^{2+}$ regulatory proteins present in the sarcoplasmic reticulum have recently been shown to be strongly involved in the pathogenesis of heart failure. Chronic activation of the sympathetic nervous system or of the renin-angiotensin system induces abnormalities in both the function and structure of these proteins. We review here the considerable body of evidence that has accumulated to support the notion that such abnormalities contribute to a defectiveness of contractile performance and hence to the progression of heart failure.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Yano, Masafumi and Ikeda, Yasuhiro and Matsuzaki, Masunori}, biburl = {https://www.bibsonomy.org/bibtex/234eca806a093034eb5cd17d932ce139b/hake}, description = {The whole bibliography file I use.}, doi = {10.1172/JCI200524159}, file = {Yano_2005_556.pdf:Yano_2005_556.pdf:PDF}, interhash = {2e361eee2dedea7cd62c1e0afd0b43d9}, intrahash = {34eca806a093034eb5cd17d932ce139b}, journal = {J. Clin. Invest.}, keywords = {15765137 Animals, Calcium Calcium, Calcium-Binding Cardiac Cardiac, Cardiomyopathy, Channel, Contraction, Gov't, Humans, Hypertrophic, Low, Muscle Myocardial Myocytes, Non-U.S. Output, Proteins, Receptor Release Research Reticulum, Ryanodine Sarcoplasmic Signaling, Support,}, month = Mar, number = 3, pages = {556--564}, pmid = {15765137}, timestamp = {2009-06-03T11:21:38.000+0200}, title = {Altered intracellular {C}a$^{2+}$ handling in heart failure.}, url = {http://dx.doi.org/10.1172/JCI200524159}, volume = 115, year = 2005 } @article{Xu_1998_2302, abstract = {The cardiac muscle sarcoplasmic reticulum {C}a$^{2+}$ release channel (ryanodine receptor) is a ligand-gated channel that is activated by micromolar cytoplasmic {C}a$^{2+}$ concentrations and inactivated by millimolar cytoplasmic {C}a$^{2+}$ concentrations. The effects of sarcoplasmic reticulum lumenal {C}a$^{2+}$ on the purified release channel were examined in single channel measurements using the planar lipid bilayer method. In the presence of caffeine and nanomolar cytosolic {C}a$^{2+}$ concentrations, lumenal-to-cytosolic {C}a$^{2+}$ fluxes >/=0.25 pA activated the channel. At the maximally activating cytosolic {C}a$^{2+}$ concentration of 4 microM, lumenal {C}a$^{2+}$ fluxes of 8 pA and greater caused a decline in channel activity. Lumenal {C}a$^{2+}$ fluxes primarily increased channel activity by increasing the duration of mean open times. Addition of the fast {C}a$^{2+}$-complexing buffer 1,2-bis(2-aminophenoxy)ethanetetraacetic acid (BAPTA) to the cytosolic side of the bilayer increased lumenal {C}a$^{2+}$-activated channel activities, suggesting that it lowered {C}a$^{2+}$ concentrations at cytosolic {C}a$^{2+}$-inactivating sites. Regulation of channel activities by lumenal {C}a$^{2+}$ could be also observed in the absence of caffeine and in the presence of 5 mM MgATP. These results suggest that lumenal {C}a$^{2+}$ can regulate cardiac {C}a$^{2+}$ release channel activity by passing through the open channel and binding to the channel's cytosolic {C}a$^{2+}$ activation and inactivation sites.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Xu, L. and Meissner, G.}, biburl = {https://www.bibsonomy.org/bibtex/20deae75665c24182a291d00c7550885e/hake}, description = {The whole bibliography file I use.}, file = {Xu_1998_2302.pdf:Xu_1998_2302.pdf:PDF}, interhash = {26270067ef72bc63d731b623147fecc5}, intrahash = {0deae75665c24182a291d00c7550885e}, journal = {Biophys. J.}, key = 215, keywords = {9788925 Acid, Adenosine Animals, Binding Blockers, Caffeine, Calcium Calcium, Calcium-Binding Cells, Channel Channel, Channels, Chimeric Cultured, Dogs, Egtazic Electrophysiology, Gov't, Heart, Humans, Immunophilins, Isoforms, Liposomes, Magnesium, Mammals, Muscle, Myocardium, Non-U.S. P.H.S., Protein Proteins, Receptor Release Research Reticulum, Ryanodine Ryanodine, Sarcoplasmic Skeletal, Support, Tacrolimus Tacrolimus, Triphosphate, Tritium, U.S.}, month = Nov, number = 5, pages = {2302--2312}, pmid = {9788925}, timestamp = {2009-06-03T11:21:38.000+0200}, title = {Regulation of cardiac muscle {C}a$^{2+}$ release channel by sarcoplasmic reticulum lumenal {C}a$^{2+}$.}, url = {http://www.biophysj.org/cgi/content/full/75/5/2302}, volume = 75, year = 1998 } @article{Wins_2000_119, abstract = {Three topics of importance to modeling the integrative function of the heart are reviewed. The first is modeling of the ventricular myocyte. Emphasis is placed on excitation-contraction coupling and intracellular {C}a$^{2+}$ handling, and the interpretation of experimental data regarding interval-force relationships. Second, data on use of diffusion tensor magnetic resonance ({DTMR}) imaging for measuring the anatomical structure of the cardiac ventricles are presented. A method for the semi-automated reconstruction of the ventricles using a combination of gradient recalled acquisition in the steady state ({GRASS}) and {DTMR} images is described. Third, we describe how these anatomically and biophysically based models of the cardiac ventricles can be implemented on parallel computers.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Winslow, R. L. and Scollan, D. F. and Holmes, A. and Yung, C. K. and Zhang, J. and Jafri, M. S.}, biburl = {https://www.bibsonomy.org/bibtex/267e0b04c1109bd617956cb4f63e3b9d1/hake}, description = {The whole bibliography file I use.}, doi = {2.1.119}, file = {Wins_2000_119.pdf:Wins_2000_119.pdf:PDF}, interhash = {9a933b55c6fbe44d1e8d630fc341b05e}, intrahash = {67e0b04c1109bd617956cb4f63e3b9d1}, journal = {Annu. Rev. Biomed. Eng.}, keywords = {11701509 Anatomic, Animals, Biomedical Calcium Cardiovascular, Channel, Contraction, Electrophysiology, Engineering, Function, Gov't, Heart Humans, Models, Myocardial Non-U.S. P.H.S., Receptor Release Research Reticulum, Ryanodine Sarcoplasmic Signaling, Support, U.S. Ventricles, Ventricular}, pages = {119--155}, pii = {2/1/119}, pmid = {11701509}, timestamp = {2009-06-03T11:21:37.000+0200}, title = {Electrophysiological modeling of cardiac ventricular function: from cell to organ.}, url = {http://dx.doi.org/2.1.119}, volume = 2, year = 2000 } @article{Will_2001_61, abstract = {RyR and InsP3R are {C}a$^{2+}$-release channels. When induced to open by the appropriate stimulus, these channels allow {C}a$^{2+}$ to leave intracellular storage organelles at an astonishing rate. Investigations of the ion-handling properties of isolated RyR channels have demonstrated that, at least in comparison to voltage-gated channels of surface membranes, these channels display limited powers of discrimination between physiologically relevant cations and this relative lack of selectivity is likely to contribute to the ability of {C}a$^{2+}$-release channels to maintain high rates of cation translocation without compromising function. A range of ion-handling properties in RyR are consistent with the proposal that this channel functions as a single-ion channel and theoretical considerations indicate that the high rates of ion translocation monitored for RyR would require the pore of such a structure to be short and possess a large capture radius. Measurements of the dimensions of regions of RyR involved in ion conduction and discrimination indicate that this is likely to be the case. In each monomer of RyR/InsP3R, residues making up the last two trans-membrane spanning domains and a luminal loop linking these two helices contribute to the formation of the channel pore. The luminal loops of both RyR and InsP3R contain amino acid sequences similar to those known to form the selectivity filter of {K}$^{+}$ channels. In addition the luminal loops of both {C}a$^{2+}$-release channels contain sequences that are likely to form helices that may be analogous to the pore helix visualised in KcsA. The correlation in structural elements of the luminal loops of RyR/InsP3R and KcsA has prompted us to speculate on the tertiary arrangement for this region of the {C}a$^{2+}$-release channels using the established structure of KcsA as a framework.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Williams, A. J. and West, D. J. and Sitsapesan, R.}, biburl = {https://www.bibsonomy.org/bibtex/20d12fffd85c08a72e4a1f35c70c73c2a/hake}, description = {The whole bibliography file I use.}, file = {Will_2001_61.pdf:Will_2001_61.pdf:PDF}, interhash = {a26ae06fcdb986f5c43be6247acfd689}, intrahash = {0d12fffd85c08a72e4a1f35c70c73c2a}, journal = {Q. Rev. Biophys.}, keywords = {11388090 Animals, Binding Calcium Calcium, Calmodulin, Channel Channel, Channels, Conformation, Cytoplasmic Gating, Gov't, Humans, Ion L-Type, Models, Molecular, Non-U.S. Nuclear, Protein Proteins, Receptor Receptors, Release Research Ryanodine Sites, Support, Tacrolimus and}, month = Feb, number = 1, pages = {61--104}, pmid = {11388090}, timestamp = {2009-06-03T11:21:37.000+0200}, title = {Light at the end of the {C}a$^{2+}$-release channel tunnel: structures and mechanisms involved in ion translocation in ryanodine receptor channels.}, volume = 34, year = 2001 } @article{Wier_2007_533, added-at = {2009-06-03T11:20:58.000+0200}, author = {Wier, Withrow Gil}, biburl = {https://www.bibsonomy.org/bibtex/2acbb0e97d6538f4ea01b6ef188deee37/hake}, description = {The whole bibliography file I use.}, doi = {10.1161/CIRCRESAHA.107.160929}, file = {Wier_2007_533.pdf:Wier_2007_533.pdf:PDF}, interhash = {db8841df8b34055a9a62ca3bca43c31d}, intrahash = {acbb0e97d6538f4ea01b6ef188deee37}, journal = {Circ. Res.}, keywords = {Action Animals; Caffeine; Calcium Calcium; Cardiac; Channel Channel; Channels, Channels; Contraction; Electric Gating; Humans; Ion Kinetics; L-Type; Membrane Myocardial Myocytes, Potentials; Receptor Release Reticulum Ryanodine Sarcoplasmic Signaling; Stimulation;}, month = Sep, number = 6, pages = {533--535}, pii = {101/6/533}, pmid = {17872469}, timestamp = {2009-06-03T11:21:37.000+0200}, title = {Gain and cardiac E-C coupling: revisited and revised.}, url = {http://dx.doi.org/10.1161/CIRCRESAHA.107.160929}, volume = 101, year = 2007 } @article{Wehr_2005_69, abstract = {Intracellular calcium release channels are present on sarcoplasmic and endoplasmic reticuli (SR, ER) of all cell types. There are two classes of these channels: ryanodine receptors (RyR) and inositol 1,4,5-trisphosphate receptors (IP3R). RyRs are required for excitation-contraction (EC) coupling in striated (cardiac and skeletal) muscles. RyRs are made up of macromolecular signaling complexes that contain large cytoplasmic domains, which serve as scaffolds for proteins that regulate the function of the channel. These regulatory proteins include calstabin1/calstabin2 (FKBP12/FKBP12.6), a 12/12.6 kDa subunit that stabilizes the closed state of the channel and prevents aberrant calcium leak from the SR. Kinases and phosphatases are targeted to RyR2 channels and modulate RyR2 function in response to extracellular signals. In the classic fight or flight stress response, phosphorylation of RyR channels by protein kinase A reduces the affinity for calstabin and activates the channels leading to increased SR calcium release. In heart failure, a cardiac insult causes a mismatch between blood supply and metabolic demands of organs. The chronically activated fight or flight response leads to leaky channels, altered calcium signaling, and contractile dysfunction and cardiac arrhythmias.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Wehrens, Xander H T and Lehnart, Stephan E and Marks, Andrew R}, biburl = {https://www.bibsonomy.org/bibtex/2ee764d785be9ee3ef93bca13dcb5cab5/hake}, description = {The whole bibliography file I use.}, doi = {10.1146/annurev.physiol.67.040403.114521}, file = {Wehr_2005_69.pdf:Wehr_2005_69.pdf:PDF}, institution = {Department of Physiology and Cellular Biophysics, Center for Molecular Cardiology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York 10032, USA. xw80@columbia.edu}, interhash = {ffb3e1beabf9e0c1a3f3ec7c06851b3f}, intrahash = {ee764d785be9ee3ef93bca13dcb5cab5}, journal = {Annu. Rev. Physiol.}, keywords = {Animals; Calcium Calcium; Cardiac Channel Humans; Intracellular Low; Membranes; Molecular Output, Receptor Release Ryanodine Structure;}, pages = {69--98}, pmid = {15709953}, timestamp = {2009-06-03T11:21:37.000+0200}, title = {Intracellular calcium release and cardiac disease.}, url = {http://dx.doi.org/10.1146/annurev.physiol.67.040403.114521}, volume = 67, year = 2005 } @article{Wang_2004_1011, abstract = {{C}a$^{2+}$ ions passing through a single or a cluster of {C}a$^{2+}$-permeable channels create microscopic, short-lived {C}a$^{2+}$ gradients that constitute the building blocks of cellular {C}a$^{2+}$ signaling. Over the last decade, imaging microdomain {C}a$^{2+}$ in muscle cells has unveiled the exquisite spatial and temporal architecture of intracellular {C}a$^{2+}$ dynamics and has reshaped our understanding of {C}a$^{2+}$ signaling mechanisms. Major advances include the visualization of "{C}a$^{2+}$ sparks" as the elementary events of {C}a$^{2+}$ release from the sarcoplasmic reticulum (SR), "{C}a$^{2+}$ sparklets" produced by openings of single {C}a$^{2+}$-permeable channels, miniature {C}a$^{2+}$ transients in single mitochondria ("marks"), and SR luminal {C}a$^{2+}$ depletion transients ("scraps"). As a model system, a cardiac myocyte contains a 3-dimensional grid of 104 spark ignition sites, stochastic activation of which summates into global {C}a$^{2+}$ transients. Tracking intermolecular coupling between single L-type {C}a$^{2+}$ channels and {C}a$^{2+}$ sparks has provided direct evidence validating the local control theory of {C}a$^{2+}$-induced {C}a$^{2+}$ release in the heart. In vascular smooth muscle myocytes, {C}a$^{2+}$ can paradoxically signal both vessel constriction (by global {C}a$^{2+}$ transients) and relaxation (by subsurface {C}a$^{2+}$ sparks). These findings shed new light on the origin of {C}a$^{2+}$ signaling efficiency, specificity, and versatility. In addition, microdomain {C}a$^{2+}$ imaging offers a novel modality that complements electrophysiological approaches in characterizing {C}a$^{2+}$ channels in intact cells.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Wang, Shi-Qiang and Wei, Chaoliang and Zhao, Guiling and Brochet, Didier X P and Shen, Jianxin and Song, Long-Sheng and Wang, Wang and Yang, Dongmei and Cheng, Heping}, biburl = {https://www.bibsonomy.org/bibtex/2c56f361c1da6abe144132ec34669481e/hake}, description = {The whole bibliography file I use.}, doi = {10.1161/01.RES.0000125883.68447.A1}, file = {Wang_2004_1011.pdf:Wang_2004_1011.pdf:PDF}, interhash = {827bf5c0bf75fa77f343ece976cf9156}, intrahash = {c56f361c1da6abe144132ec34669481e}, journal = {Circ. Res.}, key = 162, keywords = {15117829 Abstract, Acid, Agents, Animals, Araceae, CHO Calcium Calcium, Carcinoma, Cardiac, Cell Cells, Channel Channel, Channels, Chelating Chinese Confocal, Drugs, Egtazic English Expression Gating, Gene Gov't, Hamsters, Heart, Hepatocellular, Herbal, Humans, Ion L-Type, Line, Liver Medicinal, Microscopy, Mitochondria, Muscle, Myocytes, Neoplasm, Neoplasms, Neoplastic, Non-U.S. P.H.S., Patch-Clamp Plants, Profiling, RNA, Rabbits, Rats, Receptor Regulation, Release Research Reticulum, Rhizome, Ryanodine Sarcoplasmic Signaling, Smooth Smooth, Support, Techniques, Transport, Tumor, U.S. Vascular,}, month = Apr, number = 8, pages = {1011--1022}, pii = {94/8/1011}, pmid = {15117829}, timestamp = {2009-06-03T11:21:36.000+0200}, title = {Imaging microdomain {C}a$^{2+}$ in muscle cells.}, url = {http://dx.doi.org/10.1161/01.RES.0000125883.68447.A1}, volume = 94, year = 2004 } @article{Wang_2002_242, abstract = {For a single or a group of Markov channels gating reversibly, distributions of open and closed times should be the sum of positively weighted decaying exponentials. Violation of this microscopic reversibility has been demonstrated previously on a number of occasions at the single channel level, and has been attributed to possible channel coupling to external sources of free energy. Here we show that distribution of durations of {C}a$^{2+}$ release underlying {C}a$^{2+}$ sparks in intact cardiac myocytes exhibits a prominent mode at approximately 8 ms. Analysis of the cycle time for repetitive sparks at hyperactive sites revealed no intervals briefer than approximately 35 ms and a mode at approximately 90 ms. These results indicate that, regardless of whether {C}a$^{2+}$ sparks are single-channel or multi-channel in origin, they are generated by thermodynamically irreversible stochastic processes. In contrast, data from planar lipid bilayer experiments were consistent with reversible gating of RyR under asymmetric cis (4 microM) and trans {C}a$^{2+}$ (10 mM), suggesting that the irreversibility for {C}a$^{2+}$ spark genesis may reside at a supramolecular level. Modeling suggests that {C}a$^{2+}$-induced {C}a$^{2+}$ release among adjacent RyRs may couple the external energy derived from {C}a$^{2+}$ gradients across the SR to RyR gating in situ, and drive the irreversible generation of {C}a$^{2+}$ sparks.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Wang, Shi-Qiang and Song, Long-Sheng and Xu, Le and Meissner, Gerhard and Lakatta, Edward G and R�os, Eduardo and Stern, Michael D and Cheng, Heping}, biburl = {https://www.bibsonomy.org/bibtex/27c6f892361b7d1fd770315f52f1bcb79/hake}, description = {The whole bibliography file I use.}, file = {Wang_2002_242.pdf:Wang_2002_242.pdf:PDF}, interhash = {1a8004311aaf3a63ba40773e8af202e8}, intrahash = {7c6f892361b7d1fd770315f52f1bcb79}, journal = {Biophys. J.}, key = 203, keywords = {12080095 Acid, Animals, Bilayers, Calcium Calcium, Calibration, Cells, Chains, Channel, Confocal, Cultured, Dose-Response Drug, Egtazic Electrophysiology, Factors, Lipid Markov Microscopy, Myocardium, Rats, Receptor Relationship, Release Ryanodine Signal Sprague-Dawley, Thermodynamics, Time Transduction,}, month = Jul, number = 1, pages = {242--251}, pmid = {12080095}, timestamp = {2009-06-03T11:21:36.000+0200}, title = {Thermodynamically irreversible gating of ryanodine receptors in situ revealed by stereotyped duration of release in {C}a$^{2+}$ sparks.}, url = {http://www.biophysj.org/cgi/content/full/83/1/242}, volume = 83, year = 2002 } @article{Wang_2004_3979, abstract = {Intracellular {C}a$^{2+}$ release in many types of cells is mediated by ryanodine receptor {C}a$^{2+}$ release channels (Ry{RC}s) that are assembled into two-dimensional paracrystalline arrays in the endoplasmic/sarcoplasmic reticulum. However, the in situ operating mechanism of the Ry{RC} array is unknown. Here, we found that the elementary {C}a$^{2+}$ release events, {C}a$^{2+}$ sparks from individual Ry{RC} arrays in rat ventricular myocytes, exhibit quantized {C}a$^{2+}$ release flux. Analysis of the quantal property of {C}a$^{2+}$ sparks provided a view of unitary {C}a$^{2+}$ current and gating kinetics of the Ry{RC} in intact cells and revealed that spark activation involves dynamic recruitment of small, variable cohorts of Ry{RC}s. Intriguingly, interplay of Ry{RC}s in multichannel sparks renders an unusual, thermodynamically irreversible mode of channel gating that is unshared by an Ry{RC} acting solo, nor by Ry{RC}s in vitro. Furthermore, an array-based inhibitory feedback, overriding the regenerative {C}a$^{2+}$-induced {C}a$^{2+}$ release of Ry{RC}s, provides a supramolecular mechanism for the microscopic stability of intracellular {C}a$^{2+}$ signaling.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Wang, Shi Qiang and Stern, Michael D and R�os, Eduardo and Cheng, Heping}, biburl = {https://www.bibsonomy.org/bibtex/2846d2483dfa0983e9cc3f9cbe93c447d/hake}, description = {The whole bibliography file I use.}, doi = {10.1073/pnas.0306157101}, file = {Wang_2004_3979.pdf:Wang_2004_3979.pdf:PDF}, interhash = {dad20d7891666e954d8ec1724ce1e15a}, intrahash = {846d2483dfa0983e9cc3f9cbe93c447d}, journal = {Proc. Natl. Acad. Sci. U. S. A.}, key = 146, keywords = {15004280 Animals, Calcium Calcium, Cardiac, Channel, Confocal, Gov't, Membrane Microscopy, Myocytes, Non-U.S. P.H.S., Patch-Clamp Potentials, Rats, Receptor Release Research Ryanodine Support, Techniques, U.S.}, month = Mar, number = 11, pages = {3979--3984}, pii = {0306157101}, pmid = {15004280}, timestamp = {2009-06-03T11:21:36.000+0200}, title = {The quantal nature of {C}a$^{2+}$ sparks and in situ operation of the ryanodine receptor array in cardiac cells.}, url = {http://dx.doi.org/10.1073/pnas.0306157101}, volume = 101, year = 2004 } @article{Wang_2005_3017, abstract = {During calcium-induced calcium-release, the ryanodine receptor (RyR) opens and releases large amounts of calcium from the sarcoplasmic reticulum into the cytoplasm of the myocyte. Recent experiments have suggested that cooperativity between the four monomers comprising the RyR plays an important role in the dynamics of the overall receptor. Furthermore, this cooperativity can be affected by the binding of FK506 binding protein, and hence, modulated by adrenergic stimulation through the phosphorylating action of protein kinase A. This has important implications for heart failure, where it has been hypothesized that RyR hyperphosphorylation, resulting in a loss of cooperativity, can lead to a persistent leak and a reduced sarcoplasmic-reticula content. In this study, we construct a theoretical model that examines the cooperativity via the assumption of an allosteric interaction between the four subunits. We find that the level of cooperativity, regulated by the binding of FK506 binding-protein, can have a dramatic effect on the excitation-contraction coupling gain and that this gain exhibits a clear maximum. These findings are compared to currently available data from different species and allows for an evaluation of the aforementioned heart-failure scenario.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Wang, Kai and Tu, Yuhai and Rappel, Wouter-Jan and Levine, Herbert}, biburl = {https://www.bibsonomy.org/bibtex/2b4f9915f170bbd399d8a4019119d7db1/hake}, description = {The whole bibliography file I use.}, doi = {10.1529/biophysj.105.058958}, file = {Wang_2005_3017.pdf:Wang_2005_3017.pdf:PDF}, institution = {Department of Physics and Center for Theoretical Biological Physics, University of California at San Diego, La Jolla, CA, USA.}, interhash = {9c8df54a75325f8aa3a902a46afb11a4}, intrahash = {b4f9915f170bbd399d8a4019119d7db1}, journal = {Biophys. J.}, keywords = {AMP-Dependent Allosteric Animals; Binding Biophysics; Calcium Calcium; Cells; Channel; Channels; Chemical; Cyclic Diseases; Electrophysiology; Factors Heart Humans; Kinases; Mice; Models, Molecular; Muscle Myocardium; Phosphorylation; Protein Proteins; Rabbits; Rats; Receptor Release Reticulum; Ryanodine Sarcoplasmic Site; Statistical; Tacrolimus Thermodynamics; Time}, month = Nov, number = 5, pages = {3017--3025}, pii = {biophysj.105.058958}, pmid = {16126827}, timestamp = {2009-06-03T11:21:36.000+0200}, title = {Excitation-contraction coupling gain and cooperativity of the cardiac ryanodine receptor: a modeling approach.}, url = {http://dx.doi.org/10.1529/biophysj.105.058958}, volume = 89, year = 2005 } @article{Wage_1997_32463, abstract = {Isolated skeletal muscle ryanodine receptors (RyRs) complexed with the modulatory ligands, calmodulin (CaM) or 12-kDa FK506-binding protein (FKBP12), have been characterized by electron cryomicroscopy and three-dimensional reconstruction. RyRs are composed of 4 large subunits (molecular mass 565 kDa) that assemble to form a 4-fold symmetric complex that, architecturally, comprises two major substructures, a large ( approximately 80\% of the total mass) cytoplasmic assembly and a smaller transmembrane assembly. Both CaM and FKBP12 bind to the cytoplasmic assembly at sites that are 10 and 12 nm, respectively, from the putative entrance to the transmembrane ion channel. FKBP12 binds along the edge of the square-shaped cytoplasmic assembly near the face that interacts in vivo with the sarcolemma/transverse tubule membrane system, whereas CaM binds within a cleft that faces the junctional face of the sarcoplasmic reticulum membrane at the triad junction. Both ligands interact with a domain that connects directly to a cytoplasmic extension of the transmembrane assembly of the receptor, and thus might cause structural changes in the domain which in turn modulate channel gating.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Wagenknecht, T. and Radermacher, M. and Grassucci, R. and Berkowitz, J. and Xin, H. B. and Fleischer, S.}, biburl = {https://www.bibsonomy.org/bibtex/202b38bbc1049ea87d7cef95d09503f38/hake}, description = {The whole bibliography file I use.}, file = {Wage_1997_32463.pdf:Wage_1997_32463.pdf:PDF}, interhash = {11e3b31d8e4f8ac3266eb2d3afd6e17b}, intrahash = {02b38bbc1049ea87d7cef95d09503f38}, journal = {J. Biol. Chem.}, keywords = {Animals; Binding Calcium Calmodulin; Carrier Channel; Conformation; DNA-Binding Electron; Gov't, Gov't; Heat-Shock Humans; Microscopy, Muscle, Non-U.S. P.H.S.; Protein Proteins Proteins; Rabbits; Receptor Release Research Ryanodine Skeletal; Support, Tacrolimus U.S.}, month = Dec, number = 51, pages = {32463--32471}, pmid = {9405457}, timestamp = {2009-06-03T11:21:36.000+0200}, title = {Locations of calmodulin and FK506-binding protein on the three-dimensional architecture of the skeletal muscle ryanodine receptor.}, url = {http://www.jbc.org/cgi/content/full/272/51/32463}, volume = 272, year = 1997 }