%0 Journal Article %1 Diaz_2004_650 %A D�az, Mary E %A O'Neill, Stephen C %A Eisner, David A %D 2004 %J Circ. Res. %K 15031268 Action Adaptation, Animals, Arrhythmia, Artificial, Biochemical, Calc, Calcium Calcium, Cardiac Cardiac, Cardiovascular, Channel Channel, Channels, Conduction Contraction, Feedback, Fluid, Gating, Gov't, Heart Heart, Humans, Intracellular Ion Models, Muscle, Myocardial Myocardium, Myocytes, Non-U.S. Pacing, Physiological, Potentials, Pulse, Rate, Rats, Receptor Release Release, Research Reticulum, Ryanodine Sarcolemma, Sarcoplasmic Signaling, Skeletal, Support, System, Ventricles, Wistar, ium %N 5 %P 650--656 %R 10.1161/01.RES.0000119923.64774.72 %T Sarcoplasmic reticulum calcium content fluctuation is the key to cardiac alternans. %U http://dx.doi.org/10.1161/01.RES.0000119923.64774.72 %V 94 %X The aim of this work was to investigate whether beat-to-beat alternation in the amplitude of the systolic Ca$^2+$ transient (Ca$^2+$ alternans) is due to changes of sarcoplasmic reticulum (SR) Ca$^2+$ content, and if so, whether the alternans arises due to a change in the gain of the feedback controlling SR Ca$^2+$ content. We found that, in rat ventricular myocytes, stimulating with small (20 mV) depolarizing pulses produced alternans of the amplitude of the Ca$^2+$ transient. Confocal measurements showed that the larger transients resulted from propagation of Ca$^2+$ waves. SR Ca$^2+$ content (measured from caffeine-evoked membrane currents) alternated in phase with the alternans of Ca$^2+$ transient amplitude. After a large transient, if SR Ca$^2+$ content was elevated by brief exposure of the cell to a Na$^+$-free solution, then the alternans was interrupted and the next transient was also large. This shows that changes of SR Ca$^2+$ content are sufficient to produce alternans. The dependence of Ca$^2+$ transient amplitude on SR content was steeper under alternating than under control conditions. During alternation, the Ca$^2+$ efflux from the cell was also a steeper function of SR Ca$^2+$ content than under control. We attribute these steeper relationships to the fact that the larger responses in alternans depend on wave propagation and that wave propagation is a steep function of SR Ca$^2+$ content. In conclusion, alternans of systolic Ca$^2+$ appears to depend on alternation of SR Ca$^2+$ content. This, in turn results from the steep dependence on SR Ca$^2+$ content of Ca$^2+$ release and therefore Ca$^2+$ efflux from the cell as a consequence of wave propagation.

@article{Diaz_2004_650, abstract = {The aim of this work was to investigate whether beat-to-beat alternation in the amplitude of the systolic {C}a$^{2+}$ transient ({C}a$^{2+}$ alternans) is due to changes of sarcoplasmic reticulum (SR) {C}a$^{2+}$ content, and if so, whether the alternans arises due to a change in the gain of the feedback controlling SR {C}a$^{2+}$ content. We found that, in rat ventricular myocytes, stimulating with small (20 mV) depolarizing pulses produced alternans of the amplitude of the {C}a$^{2+}$ transient. Confocal measurements showed that the larger transients resulted from propagation of {C}a$^{2+}$ waves. SR {C}a$^{2+}$ content (measured from caffeine-evoked membrane currents) alternated in phase with the alternans of {C}a$^{2+}$ transient amplitude. After a large transient, if SR {C}a$^{2+}$ content was elevated by brief exposure of the cell to a {N}a$^{+}$-free solution, then the alternans was interrupted and the next transient was also large. This shows that changes of SR {C}a$^{2+}$ content are sufficient to produce alternans. The dependence of {C}a$^{2+}$ transient amplitude on SR content was steeper under alternating than under control conditions. During alternation, the {C}a$^{2+}$ efflux from the cell was also a steeper function of SR {C}a$^{2+}$ content than under control. We attribute these steeper relationships to the fact that the larger responses in alternans depend on wave propagation and that wave propagation is a steep function of SR {C}a$^{2+}$ content. In conclusion, alternans of systolic {C}a$^{2+}$ appears to depend on alternation of SR {C}a$^{2+}$ content. This, in turn results from the steep dependence on SR {C}a$^{2+}$ content of {C}a$^{2+}$ release and therefore {C}a$^{2+}$ efflux from the cell as a consequence of wave propagation.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {D�az, Mary E and O'Neill, Stephen C and Eisner, David A}, biburl = {https://www.bibsonomy.org/bibtex/2936348a5cc55bf71226c685b30299edc/hake}, description = {The whole bibliography file I use.}, doi = {10.1161/01.RES.0000119923.64774.72}, file = {Diaz_2004_650.pdf:Diaz_2004_650.pdf:PDF}, interhash = {35b323f908f15e27d9a9d7055329cd52}, intrahash = {936348a5cc55bf71226c685b30299edc}, journal = {Circ. Res.}, key = 273, keywords = {15031268 Action Adaptation, Animals, Arrhythmia, Artificial, Biochemical, Calc, Calcium Calcium, Cardiac Cardiac, Cardiovascular, Channel Channel, Channels, Conduction Contraction, Feedback, Fluid, Gating, Gov't, Heart Heart, Humans, Intracellular Ion Models, Muscle, Myocardial Myocardium, Myocytes, Non-U.S. Pacing, Physiological, Potentials, Pulse, Rate, Rats, Receptor Release Release, Research Reticulum, Ryanodine Sarcolemma, Sarcoplasmic Signaling, Skeletal, Support, System, Ventricles, Wistar, ium}, month = Mar, number = 5, pages = {650--656}, pii = {01.RES.0000119923.64774.72}, pmid = {15031268}, timestamp = {2009-06-03T11:21:10.000+0200}, title = {Sarcoplasmic reticulum calcium content fluctuation is the key to cardiac alternans.}, url = {http://dx.doi.org/10.1161/01.RES.0000119923.64774.72}, volume = 94, year = 2004 }