%0 Journal Article %1 Luky_2001_785 %A Lukyanenko, V. %A Viatchenko-Karpinski, S. %A Smirnov, A. %A Wiesner, T. F. %A Gy�rke, S. %D 2001 %J Biophys. J. %K 11463625 ATPase, Animals, Antibodies, Caffeine, Calcium Calcium, Cell Channel, Electrophysiology, Fluorescence, Gov't, Heart Ion Magnesium, Male, Membrane Monoclonal, Non-U.S. P.H.S., Patch-Clamp Permeability, Rats, Receptor Release Research Reticulum, Ryanodine Sarcoplasmic Sprague-Dawley, Support, Techniques, Tetracaine, Thapsigargin, Transport, U.S. Ventricles, {C}a$^{2+}$-Transporting %N 2 %P 785--798 %T Dynamic regulation of sarcoplasmic reticulum Ca$^2+$ content and release by luminal Ca$^2+$-sensitive leak in rat ventricular myocytes. %U http://www.biophysj.org/cgi/content/full/81/2/785 %V 81 %X In cardiac muscle, excitation-contraction (E-C) coupling is determined by the ability of the sarcoplasmic reticulum (SR) to store and release Ca$^2+$. It has been hypothesized that the Ca$^2+$ sequestration and release mechanisms might be functionally linked to optimize the E-C coupling process. To explore the relationships between the loading status of the SR and functional state of the Ca$^2+$ release mechanism, we examined the effects of changes in SR Ca$^2+$ content on spontaneous Ca$^2+$ sparks in saponin-permeabilized and patch-clamped rat ventricular myocytes. SR Ca$^2+$ content was manipulated by pharmacologically altering the capacities of either Ca$^2+$ uptake or leak. Ca$^2+$ sparks were recorded using a confocal microscope and Fluo-3 and were quantified considering missed events. SR Ca$^2+$ content was assessed by application of caffeine. Exposure of permeabilized cells to anti-phospholamban antibodies elevated the SR Ca$^2+$ content and increased the frequency of sparks. Suppression of the SR Ca$^2+$ pump by thapsigargin lowered Ca$^2+$(SR) and reduced the frequency of sparks. The ryanodine receptor (RyR) blockers tetracaine and Mg$^2+$ transiently suppressed the frequency of sparks. Upon washout of the drugs, sparking activity transiently overshot control levels. Low doses of caffeine transiently potentiated sparking activity upon application and transiently depressed the sparks upon removal. In patch-clamped cardiac myocytes, exposure to caffeine produced only a transient increase in the probability of sparks induced by depolarization. We interpret these results in terms of a novel dynamic control scheme for SR Ca$^2+$ cycling. A central element of this scheme is a luminal Ca$^2+$ sensor that links the functional activity of RyRs to the loading state of the SR, allowing cells to auto-regulate the size and functional state of their SR Ca$^2+$ pool. These results are important for understanding the regulation of intracellular Ca$^2+$ release and contractility in cardiac muscle.

@article{Luky_2001_785, abstract = {In cardiac muscle, excitation-contraction (E-C) coupling is determined by the ability of the sarcoplasmic reticulum (SR) to store and release {C}a$^{2+}$. It has been hypothesized that the {C}a$^{2+}$ sequestration and release mechanisms might be functionally linked to optimize the E-C coupling process. To explore the relationships between the loading status of the SR and functional state of the {C}a$^{2+}$ release mechanism, we examined the effects of changes in SR {C}a$^{2+}$ content on spontaneous {C}a$^{2+}$ sparks in saponin-permeabilized and patch-clamped rat ventricular myocytes. SR {C}a$^{2+}$ content was manipulated by pharmacologically altering the capacities of either {C}a$^{2+}$ uptake or leak. {C}a$^{2+}$ sparks were recorded using a confocal microscope and Fluo-3 and were quantified considering missed events. SR {C}a$^{2+}$ content was assessed by application of caffeine. Exposure of permeabilized cells to anti-phospholamban antibodies elevated the SR {C}a$^{2+}$ content and increased the frequency of sparks. Suppression of the SR {C}a$^{2+}$ pump by thapsigargin lowered [{C}a$^{2+}$](SR) and reduced the frequency of sparks. The ryanodine receptor (RyR) blockers tetracaine and {M}g$^{2+}$ transiently suppressed the frequency of sparks. Upon washout of the drugs, sparking activity transiently overshot control levels. Low doses of caffeine transiently potentiated sparking activity upon application and transiently depressed the sparks upon removal. In patch-clamped cardiac myocytes, exposure to caffeine produced only a transient increase in the probability of sparks induced by depolarization. We interpret these results in terms of a novel dynamic control scheme for SR {C}a$^{2+}$ cycling. A central element of this scheme is a luminal {C}a$^{2+}$ sensor that links the functional activity of RyRs to the loading state of the SR, allowing cells to auto-regulate the size and functional state of their SR {C}a$^{2+}$ pool. These results are important for understanding the regulation of intracellular {C}a$^{2+}$ release and contractility in cardiac muscle.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Lukyanenko, V. and Viatchenko-Karpinski, S. and Smirnov, A. and Wiesner, T. F. and Gy�rke, S.}, biburl = {https://www.bibsonomy.org/bibtex/20ea149749db7cb7b6bf489cead3671c1/hake}, description = {The whole bibliography file I use.}, file = {Luky_2001_785.pdf:Luky_2001_785.pdf:PDF}, interhash = {a8b7bcd9fd82b567b0708c7633a10d4e}, intrahash = {0ea149749db7cb7b6bf489cead3671c1}, journal = {Biophys. J.}, key = 213, keywords = {11463625 ATPase, Animals, Antibodies, Caffeine, Calcium Calcium, Cell Channel, Electrophysiology, Fluorescence, Gov't, Heart Ion Magnesium, Male, Membrane Monoclonal, Non-U.S. P.H.S., Patch-Clamp Permeability, Rats, Receptor Release Research Reticulum, Ryanodine Sarcoplasmic Sprague-Dawley, Support, Techniques, Tetracaine, Thapsigargin, Transport, U.S. Ventricles, {C}a$^{2+}$-Transporting}, month = Aug, number = 2, pages = {785--798}, pmid = {11463625}, timestamp = {2009-06-03T11:21:21.000+0200}, title = {Dynamic regulation of sarcoplasmic reticulum {C}a$^{2+}$ content and release by luminal {C}a$^{2+}$-sensitive leak in rat ventricular myocytes.}, url = {http://www.biophysj.org/cgi/content/full/81/2/785}, volume = 81, year = 2001 }