%0 Journal Article %1 Rice_1999_1871 %A Rice, J. J. %A Jafri, M. S. %A Winslow, R. L. %D 1999 %J Biophys. J. %K 10512809 Action Animals, Biological, Calcium Calcium, Car, Carlo Channel Channel, Channels, Contraction, Electric Factors, Gating, Guinea Heart In Ion Kinetics, L-Type, Method, Models, Monte Myocardial Myocardium, Patch-Clamp Pigs, Potentials, Rats, Receptor Release Reticulum, Ryanodine Sarcoplasmic Stimulation, Techniques, Time Ventricles, Vitro, diovascular, %N 4 %P 1871--1884 %T Modeling gain and gradedness of Ca$^2+$ release in the functional unit of the cardiac diadic space. %U http://www.biophysj.org/cgi/content/full/77/4/1871 %V 77 %X A model of the functional release unit (FRU) in rat cardiac muscle consisting of one dihydropyridine receptor (DHPR) and eight ryanodine receptor (RyR) channels, and the volume surrounding them, is formulated. It is assumed that no spatial Ca$^2+$ gradients exist in this volume, and that each FRU acts independently. The model is amenable to systematic parameter studies in which FRU dynamics are simulated at the channel level using Monte Carlo methods with Ca$^2+$ concentrations simulated by numerical integration of a coupled system of differential equations. Using stochastic methods, Ca$^2+$-induced Ca$^2+$ release (CICR) shows both high gain and graded Ca$^2+$ release that is robust when parameters are varied. For a single DHPR opening, the resulting RyR Ca$^2+$ release flux is insensitive to the DHPR open duration, and is determined principally by local sarcoplasmic reticulum (SR) Ca$^2+$ load, consistent with experimental data on Ca$^2+$ sparks. In addition, single RyR openings are effective in triggering Ca$^2+$ release from adjacent RyRs only when open duration is long and SR Ca$^2+$ load is high. This indicates relatively low coupling between RyRs, and suggests a mechanism that limits the regenerative spread of RyR openings. The results also suggest that adaptation plays an important modulatory role in shaping Ca$^2+$ release duration and magnitude, but is not solely responsible for terminating Ca$^2+$ release. Results obtained with the stochastic model suggest that high gain and gradedness can occur by the recruitment of independent FRUs without requiring spatial Ca$^2+$ gradients within a functional unit or cross-coupling between adjacent functional units.

@article{Rice_1999_1871, abstract = {A model of the functional release unit ({FRU}) in rat cardiac muscle consisting of one dihydropyridine receptor (DHPR) and eight ryanodine receptor (RyR) channels, and the volume surrounding them, is formulated. It is assumed that no spatial [{C}a$^{2+}$] gradients exist in this volume, and that each {FRU} acts independently. The model is amenable to systematic parameter studies in which {FRU} dynamics are simulated at the channel level using Monte Carlo methods with {C}a$^{2+}$ concentrations simulated by numerical integration of a coupled system of differential equations. Using stochastic methods, {C}a$^{2+}$-induced {C}a$^{2+}$ release (CICR) shows both high gain and graded {C}a$^{2+}$ release that is robust when parameters are varied. For a single DHPR opening, the resulting RyR {C}a$^{2+}$ release flux is insensitive to the DHPR open duration, and is determined principally by local sarcoplasmic reticulum (SR) {C}a$^{2+}$ load, consistent with experimental data on {C}a$^{2+}$ sparks. In addition, single RyR openings are effective in triggering {C}a$^{2+}$ release from adjacent RyRs only when open duration is long and SR {C}a$^{2+}$ load is high. This indicates relatively low coupling between RyRs, and suggests a mechanism that limits the regenerative spread of RyR openings. The results also suggest that adaptation plays an important modulatory role in shaping {C}a$^{2+}$ release duration and magnitude, but is not solely responsible for terminating {C}a$^{2+}$ release. Results obtained with the stochastic model suggest that high gain and gradedness can occur by the recruitment of independent {FRU}s without requiring spatial [{C}a$^{2+}$] gradients within a functional unit or cross-coupling between adjacent functional units.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Rice, J. J. and Jafri, M. S. and Winslow, R. L.}, biburl = {https://www.bibsonomy.org/bibtex/2578f5372d25beb4115708d246e523644/hake}, description = {The whole bibliography file I use.}, file = {Rice_1999_1871.pdf:Rice_1999_1871.pdf:PDF}, interhash = {6b239c888bb7ac1b9be4bd45a244e865}, intrahash = {578f5372d25beb4115708d246e523644}, journal = {Biophys. J.}, key = 152, keywords = {10512809 Action Animals, Biological, Calcium Calcium, Car, Carlo Channel Channel, Channels, Contraction, Electric Factors, Gating, Guinea Heart In Ion Kinetics, L-Type, Method, Models, Monte Myocardial Myocardium, Patch-Clamp Pigs, Potentials, Rats, Receptor Release Reticulum, Ryanodine Sarcoplasmic Stimulation, Techniques, Time Ventricles, Vitro, diovascular,}, month = Oct, number = 4, pages = {1871--1884}, pmid = {10512809}, timestamp = {2009-06-03T11:21:26.000+0200}, title = {Modeling gain and gradedness of {C}a$^{2+}$ release in the functional unit of the cardiac diadic space.}, url = {http://www.biophysj.org/cgi/content/full/77/4/1871}, volume = 77, year = 1999 }