%0 Journal Article %1 O'Ne_2004_121 %A O'Neill, S. C. %A Miller, L. %A Hinch, R. %A Eisner, D. A. %D 2004 %J J. Physiol. %K 15194743 ATPase, Action Algorithms, Animals, Calcium Calcium, Cardiac, Cardiovascular, Cell Cells, Channel Channel, Channels, Comparative Computer Computing, Conduction, Conductivity, Contraction, Cultured, Electric Electrophysiology, Enzyme Gating, Gov't, Heart Heart, Humans, Inhibitors, Ion L-Type, Magnetics, Mathematical Membrane Membrane, Models, Muscle Myocardial Myocytes, Neural Neurological, Neurons, Non-U.S. P.H.S., Potentials, Rate, Rats, Receptor Release Research Reticulum, Ryanodine Sarcolemma, Sarcoplasmic Signaling, Simulation, Sodium Study, Support, Synaptic Transmission, U.S. Ventricles, {C}a$^{2+}$-Transporting %N Pt 1 %P 121--128 %R 10.1113/jphysiol.2003.058917 %T Interplay between SERCA and sarcolemmal Ca$^2+$ efflux pathways controls spontaneous release of Ca$^2+$ from the sarcoplasmic reticulum in rat ventricular myocytes. %U http://dx.doi.org/10.1113/jphysiol.2003.058917 %V 559 %X Waves of calcium-induced calcium release occur in a variety of cell types and have been implicated in the origin of cardiac arrhythmias. We have investigated the effects of inhibiting the SR Ca$^2+$-ATPase (SERCA) with the reversible inhibitor 2',5'-di(tert-butyl)-1,4-benzohydroquinone (TBQ) on the properties of these waves. Cardiac myocytes were voltage clamped at a constant potential between -65 and -40 mV and spontaneous waves evoked by increasing external Ca$^2+$ concentration to 4 mm. Application of 100 microm TBQ decreased the frequency of waves. This was associated with increases of resting Ca$^2+$(i), the time constant of decay of Ca$^2+$(i) and the integral of the accompanying Na$^+$-Ca$^2+$ exchange current. There was also a decrease in propagation velocity of the waves. There was an increase of the calculated Ca$^2+$ efflux per wave. The SR Ca$^2+$ content when a wave was about to propagate decreased to 91.7 +/- 3.2\%. The period between waves increased in direct proportion to the Ca$^2+$ efflux per wave meaning that TBQ had no effect on the Ca$^2+$ efflux per unit time. We conclude that (i) decreased wave frequency is not a direct consequence of decreased Ca$^2+$ pumping by SERCA between waves but, rather, to more Ca$^2+$ loss on each wave; (ii) inhibiting SERCA increases the chance of spontaneous Ca$^2+$ release propagating at a given SR content.

@article{O'Ne_2004_121, abstract = {Waves of calcium-induced calcium release occur in a variety of cell types and have been implicated in the origin of cardiac arrhythmias. We have investigated the effects of inhibiting the SR {C}a$^{2+}$-ATPase (SERCA) with the reversible inhibitor 2',5'-di(tert-butyl)-1,4-benzohydroquinone (TBQ) on the properties of these waves. Cardiac myocytes were voltage clamped at a constant potential between -65 and -40 mV and spontaneous waves evoked by increasing external {C}a$^{2+}$ concentration to 4 mm. Application of 100 microm TBQ decreased the frequency of waves. This was associated with increases of resting [{C}a$^{2+}$](i), the time constant of decay of [{C}a$^{2+}$](i) and the integral of the accompanying {N}a$^{+}$-{C}a$^{2+}$ exchange current. There was also a decrease in propagation velocity of the waves. There was an increase of the calculated {C}a$^{2+}$ efflux per wave. The SR {C}a$^{2+}$ content when a wave was about to propagate decreased to 91.7 +/- 3.2\%. The period between waves increased in direct proportion to the {C}a$^{2+}$ efflux per wave meaning that TBQ had no effect on the {C}a$^{2+}$ efflux per unit time. We conclude that (i) decreased wave frequency is not a direct consequence of decreased {C}a$^{2+}$ pumping by SERCA between waves but, rather, to more {C}a$^{2+}$ loss on each wave; (ii) inhibiting SERCA increases the chance of spontaneous {C}a$^{2+}$ release propagating at a given SR content.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {O'Neill, S. C. and Miller, L. and Hinch, R. and Eisner, D. A.}, biburl = {https://www.bibsonomy.org/bibtex/2b2b4d86bc9ea4aa242432119521141dc/hake}, description = {The whole bibliography file I use.}, doi = {10.1113/jphysiol.2003.058917}, file = {O'Ne_2004_121.pdf:O'Ne_2004_121.pdf:PDF}, interhash = {d52048282bec9dca2d4a37833a6e6957}, intrahash = {b2b4d86bc9ea4aa242432119521141dc}, journal = {J. Physiol.}, key = 270, keywords = {15194743 ATPase, Action Algorithms, Animals, Calcium Calcium, Cardiac, Cardiovascular, Cell Cells, Channel Channel, Channels, Comparative Computer Computing, Conduction, Conductivity, Contraction, Cultured, Electric Electrophysiology, Enzyme Gating, Gov't, Heart Heart, Humans, Inhibitors, Ion L-Type, Magnetics, Mathematical Membrane Membrane, Models, Muscle Myocardial Myocytes, Neural Neurological, Neurons, Non-U.S. P.H.S., Potentials, Rate, Rats, Receptor Release Research Reticulum, Ryanodine Sarcolemma, Sarcoplasmic Signaling, Simulation, Sodium Study, Support, Synaptic Transmission, U.S. Ventricles, {C}a$^{2+}$-Transporting}, month = Aug, number = {Pt 1}, pages = {121--128}, pii = {jphysiol.2003.058917}, pmid = {15194743}, timestamp = {2009-06-03T11:21:24.000+0200}, title = {Interplay between SERCA and sarcolemmal {C}a$^{2+}$ efflux pathways controls spontaneous release of {C}a$^{2+}$ from the sarcoplasmic reticulum in rat ventricular myocytes.}, url = {http://dx.doi.org/10.1113/jphysiol.2003.058917}, volume = 559, year = 2004 }