%0 Journal Article %1 Bret_2005_804 %A Brette, Fabien %A Despa, Sanda %A Bers, Donald M %A Orchard, Clive H %D 2005 %J J. Mol. Cell. Cardiol. %K 16198369 Animals, Caffeine, Calcium, Cardiac, Extramural, Factors, Gov't, Heart Myocytes, N.I.H., Non-U.S. Rats, Research Reticulum, Sarcoplasmic Sprague-Dawley, Support, Time Ventricles, %N 5 %P 804--812 %R 10.1016/j.yjmcc.2005.08.005 %T Spatiotemporal characteristics of SR Ca$^2+$ uptake and release in detubulated rat ventricular myocytes. %U http://dx.doi.org/10.1016/j.yjmcc.2005.08.005 %V 39 %X In cardiac ventricular myocytes, sarcoplasmic reticulum (SR) Ca$^2+$ load is a key determinant of SR Ca$^2+$ release. This release normally occurs predominantly from SR junctions at sarcolemmal invaginations (t-tubules), ensuring synchronous SR Ca$^2+$ release throughout the cell. However under conditions of Ca$^2+$ overload, spontaneous SR Ca$^2+$ release and propagating Ca$^2+$ waves can occur, which are pro-arrhythmic. We used detubulated rat ventricular myocytes to determine the dependence of Ca$^2+$ wave propagation on SR Ca$^2+$ load, and the role of t-tubules in SR Ca$^2+$ uptake and spontaneous release. After SR Ca$^2+$ depletion, recovery of Ca$^2+$ transient amplitude (and SR Ca$^2+$ load) was slower in detubulated than control myocytes (half-maximal recovery: 9.9+/-1.4 vs. 5.5+/-0.7 beats). In detubulated myocytes the extent and velocity of Ca$^2+$ propagation from the cell periphery increased with each beat and depended steeply on SR Ca$^2+$ load. Isoproterenol (ISO) accelerated recovery, increased maximal propagation velocity and reduced the threshold SR Ca$^2+$ load for propagation. Ca$^2+$ spark frequency was uniform across control cell width and was similar at the periphery of detubulated cells. However, internal Ca$^2+$ spark frequency in detubulated cells was 75\% lower (despite comparable local SR Ca$^2+$ load); this transverse spark frequency profile was similar to that in atrial myocytes. We conclude that: (1) t-tubule Ca$^2+$ fluxes normally control SR Ca$^2+$ refilling; (2) Ca$^2+$ wave propagation depends steeply on SR Ca$^2+$ content (3) SR-t-tubule junctions are important in initiating SR Ca$^2+$ release and (4) ISO enhances propagation of SR Ca release, but not the initiation of SR Ca release events (for given SR Ca$^2+$ loads).

@article{Bret_2005_804, abstract = {In cardiac ventricular myocytes, sarcoplasmic reticulum (SR) {C}a$^{2+}$ load is a key determinant of SR {C}a$^{2+}$ release. This release normally occurs predominantly from SR junctions at sarcolemmal invaginations (t-tubules), ensuring synchronous SR {C}a$^{2+}$ release throughout the cell. However under conditions of {C}a$^{2+}$ overload, spontaneous SR {C}a$^{2+}$ release and propagating {C}a$^{2+}$ waves can occur, which are pro-arrhythmic. We used detubulated rat ventricular myocytes to determine the dependence of {C}a$^{2+}$ wave propagation on SR {C}a$^{2+}$ load, and the role of t-tubules in SR {C}a$^{2+}$ uptake and spontaneous release. After SR {C}a$^{2+}$ depletion, recovery of {C}a$^{2+}$ transient amplitude (and SR {C}a$^{2+}$ load) was slower in detubulated than control myocytes (half-maximal recovery: 9.9+/-1.4 vs. 5.5+/-0.7 beats). In detubulated myocytes the extent and velocity of {C}a$^{2+}$ propagation from the cell periphery increased with each beat and depended steeply on SR {C}a$^{2+}$ load. Isoproterenol (ISO) accelerated recovery, increased maximal propagation velocity and reduced the threshold SR {C}a$^{2+}$ load for propagation. {C}a$^{2+}$ spark frequency was uniform across control cell width and was similar at the periphery of detubulated cells. However, internal {C}a$^{2+}$ spark frequency in detubulated cells was 75\% lower (despite comparable local SR {C}a$^{2+}$ load); this transverse spark frequency profile was similar to that in atrial myocytes. We conclude that: (1) t-tubule {C}a$^{2+}$ fluxes normally control SR {C}a$^{2+}$ refilling; (2) {C}a$^{2+}$ wave propagation depends steeply on SR {C}a$^{2+}$ content (3) SR-t-tubule junctions are important in initiating SR {C}a$^{2+}$ release and (4) ISO enhances propagation of SR Ca release, but not the initiation of SR Ca release events (for given SR {C}a$^{2+}$ loads).}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Brette, Fabien and Despa, Sanda and Bers, Donald M and Orchard, Clive H}, biburl = {https://www.bibsonomy.org/bibtex/2fd4a1ab6e6259a877e4e3da742b91a12/hake}, description = {The whole bibliography file I use.}, doi = {10.1016/j.yjmcc.2005.08.005}, file = {Bret_2005_804.pdf:Bret_2005_804.pdf:PDF}, interhash = {0703d9b83974767fa70fd58fc008d088}, intrahash = {fd4a1ab6e6259a877e4e3da742b91a12}, journal = {J. Mol. Cell. Cardiol.}, keywords = {16198369 Animals, Caffeine, Calcium, Cardiac, Extramural, Factors, Gov't, Heart Myocytes, N.I.H., Non-U.S. Rats, Research Reticulum, Sarcoplasmic Sprague-Dawley, Support, Time Ventricles,}, month = Nov, number = 5, pages = {804--812}, pii = {S0022-2828(05)00259-2}, pmid = {16198369}, timestamp = {2009-06-03T11:21:06.000+0200}, title = {Spatiotemporal characteristics of SR {C}a$^{2+}$ uptake and release in detubulated rat ventricular myocytes.}, url = {http://dx.doi.org/10.1016/j.yjmcc.2005.08.005}, volume = 39, year = 2005 }