@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{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{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{Ueha_1991_651, abstract = {The effects of low (pCa 7.5 to 3) concentrations of intracellular calcium ion on a single potassium channel in the sarcoplasmic reticulum of canine heart ventricular muscle were investigated using a planar lipid bilayer technique. The low concentrations were obtained by mixing EGTA and calcium chloride. By varying the pCa of the cytoplasmic face between 3 to 7.5, two novel effects were observed. First, an increase in the intracellular {C}a$^{2+}$ concentration produced an increase in the unit current amplitude of open states; the voltage-current relationship was ohmic at these concentrations. Second, an increase in the {C}a$^{2+}$ concentration increased the open probability. Both these effects of {C}a$^{2+}$ were dose-dependent, and were consistently observed in all channels tested. Thus, the SR potassium channel observed appears to belong to the class of {C}a$^{2+}$-activated potassium channels.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Uehara, A. and Yasukohchi, M. and Ogata, S. and Imanaga, I.}, biburl = {https://www.bibsonomy.org/bibtex/24f09975660750c3bfbb6f4f62937c2e6/hake}, description = {The whole bibliography file I use.}, interhash = {a0191a355a0a4a511a65f12dd5cb3cb6}, intrahash = {4f09975660750c3bfbb6f4f62937c2e6}, journal = {Pflugers Arch}, keywords = {AMP-Dependent Acid Acid, Acids, Adenosine Algorithms, Alternative Amino Aniline Animal, Animals, Arachidonic Asparagine, Aspartic Bilayers, Binding Binding, Biological Biological, Biotransformation, Cadmium, Calcium Calcium, Carrier Cations, Cattle, Cell Cells, Channel Channels, Chimeric Chloride, Cloning, Cobalt, Competitive, Compounds, Conductivity, Conserved Cricetulus, Cultured, Cyclic Cysteine, Cytoplasm, Dogs, Dose-Response Drug, Electric Electrophysiology, Enzyme Expression, Extracellular Fibroblasts, Fura-2, Gating, Gene Hamsters, Heart Heart, Humans, Hypoxia, In Inhibitors, Intercellular Ion Junctions, Kidney Kinases, Kinetics, Knockout, Lanthanu, Ligands, Line, Lipid Lithium, Lung, Magnesium, Manganese, Membrane Membrane, Membranes, Mice, Models, Molecular Molecular, Motifs, Permeability, Potentials, Protein Proteins, Radioisotopes, Relationship, Sequence, Sites, Space, Splicing, Substitution, Transport, Triphosphate, Tubules, Ventricles, Vitro,}, month = Feb, number = 6, pages = {651--653}, pmid = {2057327}, timestamp = {2009-06-03T11:21:35.000+0200}, title = {Activation by intracellular calcium of a potassium channel in cardiac sarcoplasmic reticulum.}, volume = 417, year = 1991 } @article{Ueha_1994_195, abstract = {The modulating effects of {C}a$^{2+}$ on single {K}$^{+}$ channel currents in canine heart sarcoplasmic reticulum were studied using a planar lipid bilayer technique. The open-state probability and the unitary open-state current both decreased gradually as the {C}a$^{2+}$ concentration was reduced from pCa 3 to pCa 7.5. Each single-channel I-V curve was ohmic at any pCa: the modulating effect of {C}a$^{2+}$ within this range was voltage independent. The {C}a$^{2+}$ dose-response curves for the conductances and open probabilities were all biphasic in shape for both sides of the channel at the voltages used. However, {C}a$^{2+}$ within the pCa ranges used caused significantly more prominent activation of conductance and gating properties on the cytoplasmic side than it did on the SR luminal side. Furthermore, conductance decreased when cytoplasmic {C}a$^{2+}$ concentrations were greater than pCa 3. The I-V relation in this instance exhibited inward rectification caused by a voltage-dependent fast block. This suggests that cardiac SR {K}$^{+}$ channel currents may be activated or inhibited through various types of {C}a$^{2+}$ binding sites on and within the channels.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Uehara, A. and Yasukochi, M. and Imanaga, I.}, biburl = {https://www.bibsonomy.org/bibtex/28fd48ccb166fe844e2b48164ba84fe1b/hake}, description = {The whole bibliography file I use.}, file = {Ueha_1994_195.pdf:Ueha_1994_195.pdf:PDF}, interhash = {3e9c99ac2a5c62a9e9ed107a68e854a3}, intrahash = {8fd48ccb166fe844e2b48164ba84fe1b}, journal = {J. Mol. Cell. Cardiol.}, key = 209, keywords = {AMP-Dependent Acid Acid, Acids, Adenosine Algorithms, Alternative Amino Aniline Animal, Animals, Arachidonic Asparagine, Aspartic Bilayers, Binding Binding, Biological Biological, Biotransformation, Cadmium, Calcium Calcium, Carrier Cations, Cattle, Cell Cells, Channel Channels, Chimeric Cloning, Cobalt, Competitive, Compounds, Conductivity, Conserved Cricetulus, Cultured, Cyclic Cysteine, Cytoplasm, Data, Dogs, Dose-Response Drug, Electric Electrophysiology, Enzyme Expression, Extracellular Fibroblasts, Fura-2, Gating, Gene Hamsters, Heart Heart, Humans, Hypoxia, In Inhibitors, Intercellular Ion Junctions, Kidney Kinases, Kinetics, Knockout, Lanthanu, Ligands, Line, Lipid Lithium, Lung, Magnesium, Manganese, Membrane Membrane, Membranes, Mice, Models, Molecular Molecular, Motifs, Potentials, Protein Proteins, Radioisotopes, Relationship, Sequence Sequence, Sites, Space, Splicing, Substitution, Transport, Triphosphate, Tubules, Ventricles, Vitro,}, month = Feb, number = 2, pages = {195--202}, pii = {S0022282884710224}, pmid = {8006980}, timestamp = {2009-06-03T11:21:34.000+0200}, title = {Calcium modulation of single SR potassium channel currents in heart muscle.}, url = {http://dx.doi.org/10.1006/jmcc.1994.1022}, volume = 26, year = 1994 } @article{Ster_1998_259, added-at = {2009-06-03T11:20:58.000+0200}, author = {Stern, M. D.}, biburl = {https://www.bibsonomy.org/bibtex/2445795e64e15a17e69da4de036293b1b/hake}, description = {The whole bibliography file I use.}, file = {Ster_1998_259.pdf:Ster_1998_259.pdf:PDF}, interhash = {9213ab94a0baae22e7644f2b635bec35}, intrahash = {445795e64e15a17e69da4de036293b1b}, journal = {J. Gen. Physiol.}, key = 75, keywords = {9725889 Acid, Agents, Agonists, Algorithms, Analysis, Animal Animals, Anoxia, Biological, Blockers, Bone Bones, Calcium Calcium, Cattle, Cell Cells, Channel Channel, Channels, Chelating Clonazepam, Confocal, Cultured, Cytosol, Dietary Dyes, Dynamics, Egtazic Electric Electrophysiology, Exchanger, Feed, Feedback, Female, Fluorescence, Fluorescent Gov't, Heart, In Indoles, Kinetics, Linear Male, Meat, Membrane Microscopy, Minerals, Mitochondria, Models, Myocardium, Non-U.S. Nonlinear Oxygen, P.H.S., Patch-Clamp Potentials, Proteins, Pyrroles, Rats, Receptor Red, Regression Release Research Reticulum, Rumen, Ruthenium Ryanodine Sarcoplasmic Signaling, Size, Sodium-Calcium Soybeans, Sprague-Dawley, Stimulation, Support, Techniques, U.S. Vitro, Wistar, and}, month = Sep, number = 3, pages = {259--262}, pmid = {9725889}, timestamp = {2009-06-03T11:21:32.000+0200}, title = {Exploring local calcium feedback: trying to fool mother nature.}, url = {http://www.jgp.org/cgi/content/full/112/3/259}, volume = 112, year = 1998 } @article{Song_1997_665, abstract = {1. The exact nature of calcium sparks in the heart remains highly controversial. We sought to determine whether calcium sparks arise from a single or multiple calcium release channels/ ryanodine receptors in the sarcoplasmic reticulum (SR). If their genesis involves a calcium-coupled recruitment of multiple channels, calcium sparks might be abolished by a modest depletion of SR calcium (because of the decrease in unitary calcium flux and hence a decrease in the gain of local calcium-induced calcium release). If, on the other extreme, calcium sparks are produced despite severe SR depletion, the single-channel origin will be preferred. 2. Spontaneous calcium sparks were studied in rat ventricular myocytes using confocal microscopy and the fluorescent calcium probe fluo-3. A computer algorithm was developed to count and measure objectively calcium sparks in linescan images. 3. Thapsigargin (25-150 nM) depleted caffeine-releasable SR calcium by up to 64\%, in a dose- and time-dependent manner, without altering the resting cytosolic calcium level. During SR depletion, calcium sparks were robustly observed, albeit at reduced frequency (> or = 30\% of control) and amplitude (> or = 60\% of control). 4. Due to the reduced detectability of small sparks against noise background, the observed data would overestimate reduction in spark frequency but underestimate amplitude reduction. After correction for this detection bias, we found that the spark frequency was independent of SR load, whereas the amplitude was proportional to load. 5. We conclude that, although spark amplitude depends on SR filling status, the frequency of spark generation is independent of SR calcium load, and therefore independent of the local calcium release rate. This implies that sparks are single-channel events, or collective events that are well above threshold for local regeneration. Additionally, our results suggest that intraluminal SR calcium, at normal or low loads, does not play a major role in the regulation of on-gating of the ryanodine receptor.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Song, L. S. and Stern, M. D. and Lakatta, E. G. and Cheng, H.}, biburl = {https://www.bibsonomy.org/bibtex/2353649055d1a1697a01400e3caf38049/hake}, description = {The whole bibliography file I use.}, file = {Song_1997_665.pdf:Song_1997_665.pdf:PDF}, interhash = {8dfe2b94bf5fb2affd0baf52c67959d0}, intrahash = {353649055d1a1697a01400e3caf38049}, journal = {J. Physiol.}, keywords = {ATPase, Acid, Adamantane, Agents, Agonists, Algorithms, Analysis, Aniline Animal Animals, Anisotropy, Anoxia, Biological, Biophysics, Blockers, Bone Bones, Calcium Calcium, Cardiovascular, Cattle, Cell Cells, Channel Channel, Channels, Chelating Clonazepam, Compounds, Confocal, Contraction, Cultured, Cytosol, Dietary Dyes, Dynamics, Egtazic Electric Electrophysiology, Enzyme Exchanger, Feed, Feedback, Female, Fluorescence, Fluorescent Gov't, Heart Heart, In Indoles, Inhibitors, Ion Kinetics, Linear Male, Meat, Membrane Microscopy, Minerals, Mitochondria, Models, Myocardial Myocardium, Non-U.S. Nonlinear Oxygen, P.H.S., Patch-Clamp Potentials, Proteins, Pyrroles, Rats, Receptor Red, Regression Release Research Reticulum, Rumen, Ruthenium Ryanodine Sarcoplasmic Signal Signaling, Size, Sodium-Calcium Soybeans, Sprague-Dawley, Stimulation, Support, Techniques, Thapsigargin, Transduction, Transport, U.S. Ventricles, Vitro, Wistar, and {C}a$^{2+}$-Transporting}, month = Dec, pages = {665--675}, pmid = {9457644}, timestamp = {2009-06-03T11:21:32.000+0200}, title = {Partial depletion of sarcoplasmic reticulum calcium does not prevent calcium sparks in rat ventricular myocytes.}, url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9457644&query_hl=46}, volume = {505 ( Pt 3)}, year = 1997 } @article{Song_1998_677, abstract = {1. {C}a$^{2+}$ release flux across the sarcoplasmic reticulum (SR) during cardiac excitation-contraction coupling was investigated using a novel fluorescence method. Under whole-cell voltage-clamp conditions, rat ventricular myocytes were dialysed with a high concentration of EGTA (4.0 mM, 150 nM free {C}a$^{2+}$), to minimize the residence time of released {C}a$^{2+}$ in the cytoplasm, and a low-affinity, fast {C}a$^{2+}$ indicator, Oregon Green 488 BAPTA-5N ({OG}-5N; 1.0 mM, Kd approximately 31 microM), to optimize the detection of localized high [{C}a$^{2+}$] in release site microdomains. Confocal microscopy was employed to resolve intracellular [{C}a$^{2+}$] at high spatial and temporal resolution. 2. Analytical and numerical analyses indicated that, under conditions of high EGTA concentration, the free [{C}a$^{2+}$] change is the sum of two terms: one major term proportional to the SR release flux/{C}a$^{2+}$ influx, and the other reflecting the running integral of the released {C}a$^{2+}$. 3. Indeed, the {OG}-5N transients in EGTA-containing cells consisted of a prominent spike followed by a small pedestal. The {OG}-5N spike closely resembled the first derivative (d[{C}a$^{2+}$]/dt) of the conventional {C}a$^{2+}$ transient (with no EGTA), and mimicked the model-derived SR {C}a$^{2+}$ release function reported previously. In SR {C}a$^{2+}$-depleted cells, the {OG}-5N transient also closely followed the waveform of L-type {C}a$^{2+}$ current (ICa). Using ICa as a known source of {C}a$^{2+}$ influx, SR flux can be calibrated in vivo by a linear extrapolation of the ICa-elicited {OG}-5N signal. 4. The {OG}-5N image signal was localized to discrete release sites at the Z-line level of sarcomeres, indicating that the local {OG}-5N spike arises from '{C}a$^{2+}$ spikes' at transverse (T) tubule-SR junctions (due to the imbalance between calcium ions entering the cytosol and the buffer molecules). 5. Both peak SR release flux and total amount of released {C}a$^{2+}$ exhibited a bell-shaped voltage dependence. The temporal pattern of SR release also varied with membrane voltage: {C}a$^{2+}$ release was most synchronized and produced maximal peak release flux (4.2 mM s-1) at 0 mV; in contrast, maximal total release occurred at -20 mV (71 versus 61 microM at 0 mV), but the localized release signals were partially asynchronous. Since the maximal conventional [{C}a$^{2+}$] transient and contraction were elicited at 0 mV, it appears that not only the amount of {C}a$^{2+}$ released, but also the synchronization among release sites affects the whole-cell {C}a$^{2+}$ transient and the {C}a$^{2+}$-myofilament interaction.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Song, L. S. and Sham, J. S. and Stern, M. D. and Lakatta, E. G. and Cheng, H.}, biburl = {https://www.bibsonomy.org/bibtex/23af212a9abf42557760c3836f603437d/hake}, description = {The whole bibliography file I use.}, file = {Song_1998_677.pdf:Song_1998_677.pdf:PDF}, interhash = {d3e0a9b364b6026bb1c43a60fb9077e5}, intrahash = {3af212a9abf42557760c3836f603437d}, journal = {J. Physiol.}, keywords = {9769413 Acid, Agents, Agonists, Algorithms, Analysis, Animal Animals, Anoxia, Biological, Blockers, Bone Bones, Calcium Calcium, Cattle, Cell Cells, Channel Channel, Channels, Chelating Clonazepam, Confocal, Cultured, Cytosol, Dietary Dyes, Dynamics, Egtazic Electric Electrophysiology, Exchanger, Feed, Female, Fluorescence, Fluorescent Gov't, Heart, In Indoles, Kinetics, Linear Male, Meat, Membrane Microscopy, Minerals, Mitochondria, Models, Myocardium, Non-U.S. Nonlinear Oxygen, P.H.S., Patch-Clamp Potentials, Proteins, Pyrroles, Rats, Receptor Red, Regression Release Research Reticulum, Rumen, Ruthenium Ryanodine Sarcoplasmic Signaling, Size, Sodium-Calcium Soybeans, Sprague-Dawley, Stimulation, Support, Techniques, U.S. Vitro, Wistar, and}, month = Nov, pages = {677--691}, pmid = {9769413}, timestamp = {2009-06-03T11:21:32.000+0200}, title = {Direct measurement of SR release flux by tracking '{C}a$^{2+}$ spikes' in rat cardiac myocytes.}, url = {http://jp.physoc.org/cgi/content/full/512/3/677}, volume = {512 ( Pt 3)}, year = 1998 } @article{Soel_1999_266, abstract = {The transverse tubular system (t-system) of cardiac muscle is a structure that allows rapid propagation of excitation into the cell interior. Using 2-photon molecular excitation microscopy and digital image-processing methods, we have obtained a comprehensive overview of the t-system of rat ventricular myocytes in living cells. We show that it is possible to quantify the morphology of the t-system in terms of average local tubule diameter, branching pattern, and local abundance of the t-system by immersing living myocytes in a dextran-linked fluorescein solution. Our data suggest that previous electron microscopic examinations of t-system structure have underestimated both the geometric complexity of the t-system morphology and the fraction of cell volume occupied by the t-system (3.6\% in this species). About 40\% of tubules occur between Z-lines, and the t-tubule diameter is 255+/-0.85 nm (mean+/-SEM). The t-tubules leave the outer surface of the cell in an approximately rectangular array; however, at some points junctions between the t-tubules and the surface membrane are missing. In view of the complexity of the t-system apparent from our images, we propose that the t-system be renamed the "sarcolemmal Z rete." The methods presented here are generally applicable to the quantification of the sarcolemmal Z rete and other structures within cells by fluorescence microscopy in a variety of cell types.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Soeller, C. and Cannell, M. B.}, biburl = {https://www.bibsonomy.org/bibtex/28e46d54d739814aed194a73478ef4c16/hake}, description = {The whole bibliography file I use.}, file = {Soel_1999_266.pdf:Soel_1999_266.pdf:PDF}, interhash = {ded921384b2879a03ad3a153913574af}, intrahash = {8e46d54d739814aed194a73478ef4c16}, journal = {Circ. Res.}, key = 50, keywords = {Acetic Acid Acid, Acids, Action Activation, Adaptation, Adenosine Adhesion, Adhesions, Agents, Algorithms, Allergens, Allergic, Alternative Amino Aniline Animals, Antibodies, Antibody Antigens, Antipain, Auditory Biological Biological, Biosensing Bronchi, Butyric Cadherins, Calcium Calcium, Cardiac, Cardiovascular, Carrier Cell Cells, Channels, Cheese, Chelating Cilia, Cochlea, Communication, Comparative Compartmentation, Compounds, Computer Computer-Assisted, Conductivity, Confocal, Connexins, Crystalline, Crystallins, Culture Cultured, Cysteine Dermatophagoides, Desmosomes, Diagnostic Differentiation, Diffusion, Dogs, Dyes, Electric Electrochemistry, Electrophysiology, Endopeptidases, Enzyme Epithelial Epithelium, Epitopes, Ethylenediamines, Feasibility Feces, Feedback, Female, Fluorescein, Fluorescein-5-isothiocyanate, Fluorescence, Fluorescent Focal Imaging, Impedance, Inhibitors, Line, Membrane Membrane, Perception, Permeability, Potentials, Proteins, Sequence, Signaling, Simulation, Splicing, Stimulation, Studies, Study, Technique, Techniques, Transport, Triphosphate,}, month = Feb, number = 3, pages = {266-75}, timestamp = {2009-06-03T11:21:31.000+0200}, title = {Examination of the transverse tubular system in living cardiac rat myocytes by 2-photon microscopy and digital image-processing techniques.}, url = {http://circres.ahajournals.org/cgi/content/full/84/3/266}, volume = 84, year = 1999 } @article{Soel_2002_2396, abstract = {Using a combination of experimental and numerical approaches, we have tested two different approaches to calculating the sarcoplasmic reticulum (SR) {C}a$^{2+}$ release flux, which gives rise to cardiac muscle {C}a$^{2+}$ sparks. By using two-photon excited spot photolysis of DM-Nitrophen, known {C}a$^{2+}$ release flux time courses were generated to provide the first experimental validation of spark flux reconstruction algorithms. These artificial {C}a$^{2+}$ sparks show that it is possible to calculate the SR {C}a$^{2+}$ release waveform with reasonable accuracy, provided the flux equations reasonably reflect the properties of the experimental system. Within cardiac muscle cells, we show that {C}a$^{2+}$ flux reconstruction is complicated by the substantial dye binding to proteins, a factor that has not been adequately addressed in previous flux reconstruction algorithms. Furthermore, our numerical experiments suggest that the calculated time course of release flux inactivation based on conventional flux reconstruction algorithms is likely to be in error. We therefore developed novel algorithms based on an explicit dye binding scheme. When these algorithm were applied to evoked {C}a$^{2+}$ sparks in rat cardiac ventricular myocytes, the reconstructed {C}a$^{2+}$ release waveform peaked in ~5 ms and decayed with a halftime of approximately 5 ms. The peak flux magnitude was 7-12 pA, suggesting that sparks must arise from clusters of >15 ryanodine receptors.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Soeller, Christian and Cannell, Mark B}, biburl = {https://www.bibsonomy.org/bibtex/24bf54c0775f08851e1a5a8d22497b674/hake}, description = {The whole bibliography file I use.}, file = {Soel_2002_2396.pdf:Soel_2002_2396.pdf:PDF}, interhash = {bc5b6b1f8abc32589913a0363d0ffe58}, intrahash = {4bf54c0775f08851e1a5a8d22497b674}, journal = {Biophys. J.}, key = 294, keywords = {Acid, Action Adaptation, Algorithms, Analysis, Animals, Antibodies, Array Bilayers, Biological, Biosensing Butyric C57BL, Calcium Calcium, Cardiac, Cardiovascular, Carrier Cell Cells, Channel Channels, Communication, Comparative Computer Computer-Assisted, Conductivity, Confocal, Connexins, Contraction, Crystalline, Crystallins, Culture Cultured, Diagnostic Differentiation, Diffusion, Dyes, Electric Electrochemistry, Electrophysiology, Enhancement, Epithelial Epitopes, Feasibility Feedback, Fluorescein, Fluorescein-5-isothiocyanate, Fluorescence, Fluorescent Gap Gating, Gov't, Heart, Humans, Hybridization, I, Image Imaging, In Inbred Ion Ions, Junctions, Kinetics, L-Type, Lasers, Lens, Lipid Membrane Membrane, Mice, Microscopy, Models, Multiphoto, Multiphoton, Muscle Muscles, Myocardial Myocardium, Myocytes, Non-P.H.S., Non-U.S. Oligonucleotide Oligonucleotides, Oocytes, P.H.S., Photolysis, Photons, Physiological, Potentials, Processing, Propidium, Proteins, Sequence Signaling, Simulation, Situ Studies, Study, Techniques,}, month = May, number = 5, pages = {2396-414}, timestamp = {2009-06-03T11:21:31.000+0200}, title = {Estimation of the sarcoplasmic reticulum {C}a$^{2+}$ release flux underlying {C}a$^{2+}$ sparks.}, url = {http://www.biophysj.org/cgi/content/full/82/5/2396}, volume = 82, year = 2002 } @article{Soel_2004_141, abstract = {Cardiac excitation-contraction (E-C) coupling describes the process that links sarcolemmal {C}a$^{2+}$ influx via L-type {C}a$^{2+}$ channels to {C}a$^{2+}$ release from the sarcoplasmic reticulum via ryanodine receptors (RyRs). This process has proven difficult to study experimentally, and complete descriptions of how the cell couples surface membrane and intracellular signal transduction proteins to achieve both stable and sensitive intracellular calcium release are still lacking. Mathematical models provide a framework to test our understanding of how this is achieved. While no single model is yet capable of describing all features of cardiac E-C coupling, models of increasing complexity are revealing unexpected subtlety in the process. In particular, modelling has established a general failure of 'common-pool' models and has emphasized the requirement for 'local control' so that microscopic sub-cellular domains can separate local behaviour from the whole-cell average (common-pool) behaviour. The micro-architecture of the narrow diadic cleft in which the local control takes place is a key factor in determining local {C}a$^{2+}$ dynamics. There is still considerable uncertainty about the number of {C}a$^{2+}$ ions required to open RyRs within the cleft and various gating models have been proposed, many of which are in reasonable agreement with available experimental data. However, not all models exhibit a realistic voltage dependence of E-C coupling gain. Furthermore, it is unclear which model features are essential to producing reasonable gain properties. Thus, despite the success of local-control models in explaining many features of cardiac E-C coupling, more work will be needed to provide a sound theoretical basis of cardiac E-C coupling.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Soeller, Christian and Cannell, Mark B}, biburl = {https://www.bibsonomy.org/bibtex/2db90241bf53073a1eb387e2bce960b62/hake}, description = {The whole bibliography file I use.}, doi = {10.1016/j.pbiomolbio.2003.12.006}, file = {Soel_2004_141.pdf:Soel_2004_141.pdf:PDF}, interhash = {c1d99ac3c7a82890e99c4b3bb0956087}, intrahash = {db90241bf53073a1eb387e2bce960b62}, journal = {Prog. Biophys. Mol. Biol.}, key = 4, keywords = {15142741 Acid, Adaptation, Analysis, Animals, Array Biosensing Butyric Calcium Cardiovascular, Carrier Channel Channel, Channels, Computer Conductivity, Contraction, Crystalline, Crystallins, Diagnostic Electric Electrochemistry, Feedback, Gating, Gov't, Heart, Humans, Hybridization, Imaging, In Ion L-Type, Labeling, Lens, Membrane Models, Myocardial Non-U.S. Oligonucleotide Oligonucleotides, Photolysis, Physiological, Potentials, Proteins, Receptor Release Research Reticulum, Ryanodine Sarcoplasmic Sequence Signaling, Simulation, Situ Staining Support, Techniques, and}, number = {2-3}, pages = {141-62}, pdf = {Soel_2004_141.pdf}, pii = {S0079610704000148}, timestamp = {2009-06-03T11:21:31.000+0200}, title = {Analysing cardiac excitation-contraction coupling with mathematical models of local control.}, url = {http://dx.doi.org/10.1016/j.pbiomolbio.2003.12.006}, volume = 85, year = 2004 } @article{Smit_1998_15, abstract = {The elementary events of excitation-contraction coupling in heart muscle are {C}a$^{2+}$ sparks, which arise from one or more ryanodine receptors in the sarcoplasmic reticulum (SR). Here a simple numerical model is constructed to explore {C}a$^{2+}$ spark formation, detection, and interpretation in cardiac myocytes. This model includes {C}a$^{2+}$ release, cytosolic diffusion, resequestration by SR {C}a$^{2+}$-ATPases, and the association and dissociation of {C}a$^{2+}$ with endogenous {C}a$^{2+}$-binding sites and a diffusible indicator dye (fluo-3). Simulations in a homogeneous, isotropic cytosol reproduce the brightness and the time course of a typical cardiac {C}a$^{2+}$ spark, but underestimate its spatial size (approximately 1.1 micron vs. approximately 2.0 micron). Back-calculating [{C}a$^{2+}$]i by assuming equilibrium with indicator fails to provide a good estimate of the free {C}a$^{2+}$ concentration even when using blur-free fluorescence data. A parameter sensitivity study reveals that the mobility, kinetics, and concentration of the indicator are essential determinants of the shape of {C}a$^{2+}$ sparks, whereas the stationary buffers and pumps are less influential. Using a geometrically more complex version of the model, we show that the asymmetric shape of {C}a$^{2+}$ sparks is better explained by anisotropic diffusion of {C}a$^{2+}$ ions and indicator dye rather than by subsarcomeric inhomogeneities of the {C}a$^{2+}$ buffer and transport system. In addition, we examine the contribution of off-center confocal sampling to the variance of spark statistics.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Smith, G. D. and Keizer, J. E. and Stern, M. D. and Lederer, W. J. and Cheng, H.}, biburl = {https://www.bibsonomy.org/bibtex/2f49363af4da096ec89d489f6ae8c4925/hake}, description = {The whole bibliography file I use.}, file = {Smit_1998_15.pdf:Smit_1998_15.pdf:PDF}, interhash = {5784aca2aaa87ec04645e089c003d1c2}, intrahash = {f49363af4da096ec89d489f6ae8c4925}, journal = {Biophys. J.}, key = 76, keywords = {9649364 ATPase, Acid, Agents, Agonists, Algorithms, Analysis, Aniline Animal Animals, Anisotropy, Anoxia, Biological, Biophysics, Blockers, Bone Bones, Calcium Calcium, Cardiovascular, Cattle, Cell Cells, Channel Channel, Channels, Chelating Clonazepam, Compounds, Confocal, Contraction, Cultured, Cytosol, Dietary Dyes, Dynamics, Egtazic Electric Electrophysiology, Exchanger, Feed, Feedback, Female, Fluorescence, Fluorescent Gov't, Heart, In Indoles, Ion Kinetics, Linear Male, Meat, Membrane Microscopy, Minerals, Mitochondria, Models, Myocardial Myocardium, Non-U.S. Nonlinear Oxygen, P.H.S., Patch-Clamp Potentials, Proteins, Pyrroles, Rats, Receptor Red, Regression Release Research Reticulum, Rumen, Ruthenium Ryanodine Sarcoplasmic Signal Signaling, Size, Sodium-Calcium Soybeans, Sprague-Dawley, Stimulation, Support, Techniques, Transduction, Transport, U.S. Vitro, Wistar, Xanthenes, and {C}a$^{2+}$-Transporting}, month = Jul, number = 1, pages = {15--32}, pmid = {9649364}, timestamp = {2009-06-03T11:21:31.000+0200}, title = {A simple numerical model of calcium spark formation and detection in cardiac myocytes.}, url = {http://www.biophysj.org/cgi/content/full/75/1/15}, volume = 75, year = 1998 } @article{Reng_2002_2511, abstract = {In striated muscles, intracellular {C}a$^{2+}$ release is tightly controlled by the membrane voltage sensor. {C}a$^{2+}$ ions are necessary mediators of this control in cardiac but not in skeletal muscle, where their role is ill-understood. An intrinsic gating oscillation of {C}a$^{2+}$ release-not involving the voltage sensor-is demonstrated in frog skeletal muscle fibers under voltage clamp. A Markov model of the {C}a$^{2+}$ release units is shown to reproduce the oscillations, and it is demonstrated that for Markov processes to have oscillatory transients, its transition rates must violate thermodynamic reversibility. Such irreversibility results in permanent cycling of the units through a ring of states, which requires a source of free energy. Inhibition of the oscillation by 20 to 40 mM EGTA or partial depletion of {C}a$^{2+}$ in the sarcoplasmic reticulum (SR) identifies the SR [{C}a$^{2+}$] gradient as the energy source, and indicates a location of the critical {C}a$^{2+}$-sensing site at distances greater than 35 nm from the open channel. These results, which are consistent with a recent demonstration of irreversibility in gating of cardiac {C}a$^{2+}$ sparks, (Wang, S.-Q., L.-S. Song, L. {X}u, G. Meissner, E. G. Lakatta, E. R�os, M. D. Stern, and H. Cheng. 2002. Biophys. J. 83:242-251) exemplify a cell-wide oscillation caused by coupling between ion permeation and channel gating.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Rengifo, Juliana and Rosales, Rafael and Gonz�lez, Adom and Cheng, Heping and Stern, Michael D and R�os, Eduardo}, biburl = {https://www.bibsonomy.org/bibtex/287fb242b08a4ddeee1efb3dad381ccde/hake}, description = {The whole bibliography file I use.}, file = {Reng_2002_2511.pdf:Reng_2002_2511.pdf:PDF}, interhash = {23ac183c6a6abbacdf1ed9d8e21cdad6}, intrahash = {87fb242b08a4ddeee1efb3dad381ccde}, journal = {Biophys. J.}, key = 248, keywords = {12414685 Acid, Agents, Algorithms, Animals, Biophysics, Calcium Calcium, Chains, Channel, Chelating Dose-Response Drug, Egtazic Factors, Gov't, Markov Models, Muscles, Oscillometry, P.H.S., Rana Receptor Relationship, Release Research Reticulum, Ryanodine Sarcoplasmic Statistical, Support, Thermodynamics, Tim, U.S. e pipiens,}, month = Nov, number = 5, pages = {2511--2521}, pmid = {12414685}, timestamp = {2009-06-03T11:21:26.000+0200}, title = {Intracellular {C}a$^{2+}$ release as irreversible Markov process.}, url = {http://www.biophysj.org/cgi/content/full/83/5/2511}, volume = 83, year = 2002 } @article{Pape_1998_263, abstract = {Resting sarcoplasmic reticulum (SR) Ca content ([CaSR]R) was varied in cut fibers equilibrated with an internal solution that contained 20 mM EGTA and 0-1.76 mM Ca. SR Ca release and [CaSR]R were measured with the EGTA-phenol red method (. J. Gen. Physiol. 106:259-336). After an action potential, the fractional amount of Ca released from the SR increased from 0.17 to 0.50 when [CaSR]R was reduced from 1, 200 to 140 microM. This increase was associated with a prolongation of release (final time constant, from 1-2 to 10-15 ms) and of the action potential (by 1-2 ms). Similar changes in release were observed with brief stimulations to -20 mV in voltage-clamped fibers, in which charge movement (Qcm) could be measured. The peak values of Qcm and the fractional rate of SR Ca release, as well as their {ON} time courses, were little affected by reducing [CaSR]R from 1,200 to 140 microM. After repolarization, however, the {OFF} time courses of Qcm and the rate of SR Ca release were slowed by factors of 1.5-1.7 and 6.5, respectively. These and other results suggest that, after action potential stimulation of fibers in normal physiological condition, the increase in myoplasmic free [Ca] that accompanies SR Ca release exerts three negative feedback effects that tend to reduce additional release: (a) the action potential is shortened by current through Ca-activated potassium channels in the surface and/or tubular membranes; (b) the {OFF} kinetics of Qcm is accelerated; and (c) Ca inactivation of Ca release is increased. Some of these effects of Ca on an SR Ca channel or its voltage sensor appear to be regulated by the value of [Ca] within 22 nm of the mouth of the channel.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Pape, P. C. and Jong, D. S. and Chandler, W. K.}, biburl = {https://www.bibsonomy.org/bibtex/24ef4f7b879976f6b5336b7b4b56fd369/hake}, description = {The whole bibliography file I use.}, file = {Pape_1998_263.pdf:Pape_1998_263.pdf:PDF}, interhash = {2d718695e0266f15f195682dea49992c}, intrahash = {4ef4f7b879976f6b5336b7b4b56fd369}, journal = {J. Gen. Physiol.}, key = 77, keywords = {9725888 Acid, Action Agents, Animals, Anura, Buffers, Calcium Calcium, Channel Channels, Chelating Contraction, Egtazic Factors, Fibers, Gating, Gov't, Ion Kinetics, Mathematics, Muscle P.H.S., Patch-Clamp Potentials, Research Reticulum, Sarcoplasmic Support, Techniques, Time U.S.}, month = Sep, number = 3, pages = {263--295}, pmid = {9725888}, timestamp = {2009-06-03T11:21:25.000+0200}, title = {Effects of partial sarcoplasmic reticulum calcium depletion on calcium release in frog cut muscle fibers equilibrated with 20 mM EGTA.}, url = {http://www.jgp.org/cgi/content/full/112/3/263}, volume = 112, year = 1998 } @article{Okad_2005_C510, abstract = {To investigate the characteristics and underlying mechanisms of {C}a$^{2+}$ wave propagation, we developed a three-dimensional (3-D) simulator of cardiac myocytes, in which the sarcolemma, myofibril, and Z-line structure with {C}a$^{2+}$ release sites were modeled as separate structures using the finite element method. Similarly to previous studies, we assumed that {C}a$^{2+}$ diffusion from one release site to another and {C}a$^{2+}$-induced {C}a$^{2+}$ release were the basic mechanisms, but use of the finite element method enabled us to simulate not only the wave propagation in 3-D space but also the active shortening of the myocytes. Therefore, in addition to the dependence of the {C}a$^{2+}$ wave propagation velocity on the sarcoplasmic reticulum {C}a$^{2+}$ content and affinity of troponin C for {C}a$^{2+}$, we were able to evaluate the influence of active shortening on the propagation velocity. Furthermore, if the initial {C}a$^{2+}$ release took place in the proximity of the nucleus, spiral {C}a$^{2+}$ waves evolved and spread in a complex manner, suggesting that this phenomenon has the potential for arrhythmogenicity. The present 3-D simulator, with its ability to study the interaction between {C}a$^{2+}$ waves and contraction, will serve as a useful tool for studying the mechanism of this complex phenomenon.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {ichi Okada, Jun and Sugiura, Seiryo and Nishimura, Satoshi and Hisada, Toshiaki}, biburl = {https://www.bibsonomy.org/bibtex/2c5bd90eee54c7c924d785b572123fd1b/hake}, description = {The whole bibliography file I use.}, doi = {10.1152/ajpcell.00261.2004}, file = {Okad_2005_C510.pdf:Okad_2005_C510.pdf:PDF}, interhash = {de471d9ec16467743826900b12ad4c83}, intrahash = {c5bd90eee54c7c924d785b572123fd1b}, journal = {Am. J. Physiol. Cell Physiol.}, key = 124, keywords = {(Genetics), 15496481 3' Abstract, Acid, Agents, Animals, Anti-Bacterial Bacteria, Bacterial, Base Biological, Calcium Calcium, Cardiac, Complementary, Conserved Contraction, DNA, Drug English Escherichia Factors, Genetic, Genome, Genomics, Gov't, Gram-Negative Gram-Positive Human, Humans, Imaging, Initiation Mathematics, Methicillin Mice, Microbial Models, Muscle Myocytes, Non-U.S. Ofloxacin, Promoter Proteins, RNA RNA, Rats, Regions Regions, Regulatory Research Resistance, Ribonucleic Sensitivity Sequence, Sequences, Signaling, Site, Splicing, Staphylococcus Support, Terminator Tests, Three-Dimensional, Time Transcription Transcription, Untran, Untranslated, aureus, coli, slated}, month = Mar, number = 3, pages = {C510--C522}, pii = {00261.2004}, pmid = {15496481}, timestamp = {2009-06-03T11:21:24.000+0200}, title = {Three-dimensional simulation of calcium waves and contraction in cardiomyocytes using the finite element method.}, url = {http://dx.doi.org/10.1152/ajpcell.00261.2004}, volume = 288, year = 2005 } @article{Nara_1997_6961, abstract = {Immobile and mobile calcium buffers shape the calcium signal close to a channel by reducing and localizing the transient calcium increase to physiological compartments. In this paper, we focus on the impact of mobile buffers in shaping steady-state calcium gradients in the vicinity of an open channel, i.e. within its "calcium microdomain." We present a linear approximation of the combined reaction-diffusion problem, which can be solved explicitly and accounts for an arbitrary number of calcium buffers, either endogenous or added exogenously. It is valid for small saturation levels of the present buffers and shows that within a few hundred nanometers from the channel, standing calcium gradients develop in hundreds of microseconds after channel opening. It is shown that every buffer can be assigned a uniquely defined length-constant as a measure of its capability to buffer calcium close to the channel. The length-constant clarifies intuitively the significance of buffer binding and unbinding kinetics for understanding local calcium signals. Hence, we examine the parameters shaping these steady-state gradients. The model can be used to check the expected influence of single channel calcium microdomains on physiological processes such as excitation-secretion coupling or excitation-contraction coupling and to explore the differential effect of kinetic buffer parameters on the shape of these microdomains.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Naraghi, M. and Neher, E.}, biburl = {https://www.bibsonomy.org/bibtex/27850412977e7716263414551e9e6e3fb/hake}, description = {The whole bibliography file I use.}, file = {Nara_1997_6961.pdf:Nara_1997_6961.pdf:PDF}, interhash = {2c6ecefe0df4a352f5108f47ec9e469e}, intrahash = {7850412977e7716263414551e9e6e3fb}, journal = {J. Neurosci.}, key = 48, keywords = {9278532 Acetic Acid, Acids, Adenosine Adrenal Agents, Animals, Binding Biological, Buffers, Calcium Calcium, Cattle, Cells, Channels, Chelating Chromaffin Cultured, Cytosol, Diffusion, Egtazic Ethylenediamines, Fluorescence, Gov't, Kinetics, Medulla, Microscopy, Models, Non-U.S. Photochemistry, Photolysis, Research Signal Sites, Support, Synaptic Theoretical, Transduction, Transmission, Triphosphate,}, month = Sep, number = 18, pages = {6961-73}, timestamp = {2009-06-03T11:21:23.000+0200}, title = {Linearized buffered {C}a$^{2+}$ diffusion in microdomains and its implications for calculation of [{C}a$^{2+}$] at the mouth of a calcium channel.}, url = {http://www.jneurosci.org/cgi/content/full/17/18/6961}, volume = 17, year = 1997 } @article{Meis_2004_621, abstract = {The release of {C}a$^{2+}$ ions from intracellular stores is a key step in a wide variety of cellular functions. In striated muscle, the release of {C}a$^{2+}$ from the sarcoplasmic reticulum (SR) leads to muscle contraction. {C}a$^{2+}$ release occurs through large, high-conductance {C}a$^{2+}$ release channels, also known as ryanodine receptors (RyRs) because they bind the plant alkaloid ryanodine with high affinity and specificity. The RyRs are isolated as 30S protein complexes comprised of four 560 kDa RyR2 subunits and four 12 kDa FK506 binding protein ({FKBP}12) subunits. Multiple endogenous effector molecules and posttranslational modifications regulate the RyRs. This review focuses on current research toward understanding the control of the isolated cardiac {C}a$^{2+}$ release channel/ryanodine receptor (RyR2) by {C}a$^{2+}$, calmodulin, thiol oxidation/reduction and nitrosylation, and protein phosphorylation.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Meissner, Gerhard}, biburl = {https://www.bibsonomy.org/bibtex/2d84152625b6c5b18fab96bf7376df0b9/hake}, description = {The whole bibliography file I use.}, doi = {10.1016/j.ceca.2004.01.015}, file = {Meis_2004_621.pdf:Meis_2004_621.pdf:PDF}, interhash = {4d96d2099d4a5797c787e7bc2779faf8}, intrahash = {d84152625b6c5b18fab96bf7376df0b9}, journal = {Cell Calcium}, key = 223, keywords = {(Psychology), Acid Acid, Acids, Amino Animals, Binding Binding, Calcium Calcium, Calmodulin, Cell Cells, Channel Channel, Classical, Comple, Conditioning, DNA, Data, Devices, Differentiation, Diseases, Epithelial Epithelium Extinction Eye Eye, Factor, Factors, Female, Fusion Gating, Glial Gov't, Graft Growth Homology, Humans, Ion Ions, Iris, Iron, Isoforms, Learning, Line, Line-Derived Long-Evans, Macaca Male, Membrane, Molecular Motion Motor Movement, Movements, Muscle, Mutation, Myocardium, Neostriatum, Nerve Neurodegenerative Neuronal Neurotrophic Non-P.H.S., Non-U.S. P.H.S., Peptides, Perception, Phosphorylation, Photic Pigment Plasticity, Potassium, Protective Protein Proteins, Rabbits, Rats, Receptor Recombinant Reference Reflex, Release Research Reversal Ryanodine Separation, Sequence Sequence, Sites, Skeletal, Skills, Stereotaxic Stimulation, Structure, Support, Survival, Values, mulatta, of}, month = Jun, number = 6, pages = {621--628}, pii = {S0143416004000235}, pmid = {15110152}, timestamp = {2009-06-03T11:21:22.000+0200}, title = {Molecular regulation of cardiac ryanodine receptor ion channel.}, url = {http://dx.doi.org/10.1016/j.ceca.2004.01.015}, volume = 35, year = 2004 } @article{Masu_2001_39727, abstract = {Ryanodine, a plant alkaloid, is one of the most widely used pharmacological probes for intracellular {C}a$^{2+}$ signaling in a variety of muscle and non-muscle cells. Upon binding to the {C}a$^{2+}$ release channel (ryanodine receptor), ryanodine causes two major changes in the channel: a reduction in single-channel conductance and a marked increase in open probability. The molecular mechanisms underlying these alterations are not well understood. In the present study, we investigated the gating behavior and {C}a$^{2+}$ dependence of the wild type (wt) and a mutant cardiac ryanodine receptor (RyR2) after being modified by ryanodine. Single-channel studies revealed that the ryanodine-modified wt RyR2 channel was sensitive to inhibition by {M}g$^{2+}$ and to activation by caffeine and ATP. In the presence of {M}g$^{2+}$, the ryanodine-modified single wt RyR2 channel displayed a sigmoidal {C}a$^{2+}$ dependence with an EC(50) value of 110 nm, whereas the ryanodine-unmodified single wt channel exhibited an EC(50) of 120 microm for {C}a$^{2+}$ activation, indicating that ryanodine is able to increase the sensitivity of the wt RyR2 channel to {C}a$^{2+}$ activation by approximately 1,000-fold. Furthermore, ryanodine is able to restore {C}a$^{2+}$ activation and ligand response of the E3987A mutant RyR2 channel that has been shown to exhibit approximately 1,000-fold reduction in {C}a$^{2+}$ sensitivity to activation. The E3987A mutation, however, affects neither [(3)H]ryanodine binding to, nor the stimulatory and inhibitory effects of ryanodine on, the RyR2 channel. These results demonstrate that ryanodine does not "lock" the RyR channel into an open state as generally believed; rather, it sensitizes dramatically the channel to activation by {C}a$^{2+}$.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Masumiya, H. and Li, P. and Zhang, L. and Chen, S. R.}, biburl = {https://www.bibsonomy.org/bibtex/2d0197cd8b75e71c0cc59bed2183ea56f/hake}, description = {The whole bibliography file I use.}, doi = {10.1074/jbc.M106557200}, interhash = {f7773efa18f64eed37bd25659c42da71}, intrahash = {d0197cd8b75e71c0cc59bed2183ea56f}, journal = {J. Biol. Chem.}, keywords = {11507100 Acid, Alanine, Caffeine, Calcium Calcium, Channel Channel, Dose-Response Drug, Gating, Glutamic Gov't, Humans, Ion Magnesium, Mutation, Non-U.S. Receptor Relationship, Release Research Ryanodine Ryanodine, Support,}, month = Oct, number = 43, pages = {39727--39735}, pii = {M106557200}, pmid = {11507100}, timestamp = {2009-06-03T11:21:22.000+0200}, title = {Ryanodine sensitizes the {C}a$^{2+}$ release channel (ryanodine receptor) to {C}a$^{2+}$ activation.}, url = {http://dx.doi.org/10.1074/jbc.M106557200}, volume = 276, year = 2001 } @article{Liu_2001_6104, abstract = {Recombinant type 3 ryanodine receptor (RyR3) has been purified in quantities sufficient for structural characterization by cryoelectron microscopy and three-dimensional (3D) reconstruction. Two c{DNA}s were prepared and expressed in HEK293 cells, one encoding the wild-type RyR3 and the other encoding RyR3 containing glutathione S-transferase ({GST}) fused to its amino terminus ({GST}-RyR3). RyR3 was purified from detergent-solubilized transfected cells by affinity chromatography using 12.6-kDa FK506-binding protein in the form of a {GST} fusion as the affinity ligand. Purification of {GST}-RyR3 was achieved by affinity chromatography by using glutathione-Sepharose. Purified recombinant RyR3 and {GST}-RyR3 proteins exhibited high-affinity [(3)H]ryanodine binding that was sensitive to activation by {C}a$^{2+}$ and caffeine and to inhibition by {M}g$^{2+}$. 3D reconstructions of both recombinant RyR3 and {GST}-RyR3 appeared very similar to that of the native RyR3 purified from bovine diaphragm. Comparison of the 3D reconstructions of RyR3 and {GST}-RyR3 revealed that the {GST} domains and, hence, the amino termini of the RyR3 subunits are located in the "clamp" structures that form the corners of the square-shaped cytoplasmic region of homotetrameric RyR3. This study describes the 3D reconstruction of a recombinant ryanodine receptor and it demonstrates the potential of this technology for characterizing functional and structural perturbations introduced by site-directed mutagenesis.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Liu, Z. and Zhang, J. and Sharma, M. R. and Li, P. and Chen, S. R. and Wagenknecht, T.}, biburl = {https://www.bibsonomy.org/bibtex/20a1e5bdb2a6cef954ce4aca06a2a4862/hake}, description = {The whole bibliography file I use.}, doi = {10.1073/pnas.111382798}, file = {Liu_2001_6104.pdf:Liu_2001_6104.pdf:PDF}, interhash = {ea198676702a3cec4707da9fcf89eb46}, intrahash = {0a1e5bdb2a6cef954ce4aca06a2a4862}, journal = {Proc. Natl. Acad. Sci. U. S. A.}, keywords = {11353864 Acid, Adenosine Alanine, Animals, Caffeine, Calcium Calcium, Cell Channel Channel, Co, Conformation, Cryoelectron Dose-Response Drug, Electrophysiology, Fusion Gating, Gl, Glutamic Glutathione Gov't, Heart, Humans, Ion Line, Magnesium, Mice, Microscopy, Muscle Mutation, Non-U.S. P.H.S., Point Protein Proteins, Receptor Recombinant Relationship, Release Research Reticulum, Ryanodine Ryanodine, Sarcoplasmic Support, Transfection, Transferase, Triphosphate, U.S. ntraction, utamic}, month = May, number = 11, pages = {6104--6109}, pii = {111382798}, pmid = {11353864}, timestamp = {2009-06-03T11:21:20.000+0200}, title = {Three-dimensional reconstruction of the recombinant type 3 ryanodine receptor and localization of its amino terminus.}, url = {http://dx.doi.org/10.1073/pnas.111382798}, volume = 98, year = 2001 }