%0 Journal Article %1 Luky_1999_173 %A Lukyanenko, V. %A Subramanian, S. %A Gyorke, I. %A Wiesner, T. F. %A Gyorke, S. %D 1999 %J J. Physiol. %K -Transporting 10373699 ATPase, Algorithms, Anesthetics, Aniline Animals, Bilayers, Biological, Caffeine, Calcium, Central Compounds, Computer Confocal, Cytosol, Dyes, Electrophysiology, Enzyme Fluorescent Gov't, Heart, Inhibitors, Lipid Local, Microscopy, Models, Myocardium, Nervous Non-U.S. P.H.S., Rats, Research Reticulum, Sarcoplasmic Simulation, Sprague-Dawley, Stimulants, Support, System Thapsigargin, U.S. Xanthenes, {C}a$^{2+}$, %P 173--186 %T The role of luminal Ca$^2+$ in the generation of Ca$^2+$ waves in rat ventricular myocytes. %U http://jp.physoc.org/cgi/content/full/518/1/173 %V 518 ( Pt 1) %X 1. We used confocal Ca$^2+$ imaging and fluo-3 to investigate the transition of localized Ca$^2+$ releases induced by focal caffeine stimulation into propagating Ca$^2+$ waves in isolated rat ventricular myocytes. 2. Self-sustaining Ca$^2+$ waves could be initiated when the cellular Ca$^2+$ load was increased by elevating the extracellular Ca$^2+$ (Ca$^2+$o) and they could also be initiated at normal Ca$^2+$ loads when the sensitivity of the release sites to cytosolic Ca$^2+$ was enhanced by low doses of caffeine. When we prevented the accumulation of extra Ca$^2+$ in the luminal compartment of the sarcoplasmic reticulum (SR) with thapsigargin, focal caffeine pulses failed to trigger self-sustaining Ca$^2+$ waves on elevation of Ca$^2+$o. Inhibition of SR Ca$^2+$ uptake by thapsigargin in cells already preloaded with Ca$^2+$ above normal levels did not prevent local Ca$^2+$ elevations from triggering propagating waves. Moreover, wave velocity increased by 20 \%. Tetracaine (0.75 mM) caused transient complete inhibition of both local and propagating Ca$^2+$ signals, followed by full recovery of the responses due to increased SR Ca$^2+$ accumulation. 3. Computer simulations using a numerical model with spatially distinct Ca$^2+$ release sites suggested that increased amounts of releasable Ca$^2+$ might not be sufficient to generate self-sustaining Ca$^2+$ waves under conditions of Ca$^2+$ overload unless the threshold of release site Ca$^2+$ activation was set at relatively low levels (< 1.5 microM). 4. We conclude that the potentiation of SR Ca$^2+$ release channels by luminal Ca$^2+$ is an important factor in Ca$^2+$ wave generation. Wave propagation does not require the translocation of Ca$^2+$ from the spreading wave front into the SR. Instead, it relies on luminal Ca$^2+$ sensitizing Ca$^2+$ release channels to cytosolic Ca$^2+$.

@article{Luky_1999_173, abstract = {1. We used confocal {C}a$^{2+}$ imaging and fluo-3 to investigate the transition of localized {C}a$^{2+}$ releases induced by focal caffeine stimulation into propagating {C}a$^{2+}$ waves in isolated rat ventricular myocytes. 2. Self-sustaining {C}a$^{2+}$ waves could be initiated when the cellular {C}a$^{2+}$ load was increased by elevating the extracellular [{C}a$^{2+}$] ([{C}a$^{2+}$]o) and they could also be initiated at normal {C}a$^{2+}$ loads when the sensitivity of the release sites to cytosolic {C}a$^{2+}$ was enhanced by low doses of caffeine. When we prevented the accumulation of extra {C}a$^{2+}$ in the luminal compartment of the sarcoplasmic reticulum (SR) with thapsigargin, focal caffeine pulses failed to trigger self-sustaining {C}a$^{2+}$ waves on elevation of [{C}a$^{2+}$]o. Inhibition of SR {C}a$^{2+}$ uptake by thapsigargin in cells already preloaded with {C}a$^{2+}$ above normal levels did not prevent local {C}a$^{2+}$ elevations from triggering propagating waves. Moreover, wave velocity increased by 20 \%. Tetracaine (0.75 mM) caused transient complete inhibition of both local and propagating {C}a$^{2+}$ signals, followed by full recovery of the responses due to increased SR {C}a$^{2+}$ accumulation. 3. Computer simulations using a numerical model with spatially distinct {C}a$^{2+}$ release sites suggested that increased amounts of releasable {C}a$^{2+}$ might not be sufficient to generate self-sustaining {C}a$^{2+}$ waves under conditions of {C}a$^{2+}$ overload unless the threshold of release site {C}a$^{2+}$ activation was set at relatively low levels (< 1.5 microM). 4. We conclude that the potentiation of SR {C}a$^{2+}$ release channels by luminal {C}a$^{2+}$ is an important factor in {C}a$^{2+}$ wave generation. Wave propagation does not require the translocation of {C}a$^{2+}$ from the spreading wave front into the SR. Instead, it relies on luminal {C}a$^{2+}$ sensitizing {C}a$^{2+}$ release channels to cytosolic {C}a$^{2+}$.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Lukyanenko, V. and Subramanian, S. and Gyorke, I. and Wiesner, T. F. and Gyorke, S.}, biburl = {https://www.bibsonomy.org/bibtex/277171ba0a9c31159dd76a818a8a364e4/hake}, description = {The whole bibliography file I use.}, file = {Luky_1999_173.pdf:Luky_1999_173.pdf:PDF}, interhash = {b457c1b3d11f201947d11737245cce39}, intrahash = {77171ba0a9c31159dd76a818a8a364e4}, journal = {J. Physiol.}, key = 235, keywords = {-Transporting 10373699 ATPase, Algorithms, Anesthetics, Aniline Animals, Bilayers, Biological, Caffeine, Calcium, Central Compounds, Computer Confocal, Cytosol, Dyes, Electrophysiology, Enzyme Fluorescent Gov't, Heart, Inhibitors, Lipid Local, Microscopy, Models, Myocardium, Nervous Non-U.S. P.H.S., Rats, Research Reticulum, Sarcoplasmic Simulation, Sprague-Dawley, Stimulants, Support, System Thapsigargin, U.S. Xanthenes, {C}a$^{2+}$,}, month = Jul, pages = {173--186}, pii = {PHY_9246}, pmid = {10373699}, timestamp = {2009-06-03T11:21:21.000+0200}, title = {The role of luminal {C}a$^{2+}$ in the generation of {C}a$^{2+}$ waves in rat ventricular myocytes.}, url = {http://jp.physoc.org/cgi/content/full/518/1/173}, volume = {518 ( Pt 1)}, year = 1999 }