%0 Journal Article %1 Harr_2005_543 %A Harris, David M %A Mills, Geoffrey D %A Chen, Xiongwen %A Kubo, Hajime %A Berretta, Remus M %A Votaw, V. Scott %A Santana, Luis F %A Houser, Steven R %D 2005 %J Circ. Res. %K Action Animals; Aortic Calcium Calcium; Cardiac; Cats; Congestive; Constriction, Contraction; Diseases; Failure, Heart Hypertrophy, Ion Left Myocardial Myocytes, Patch-Clamp Pathologic; Potentials; Reticulum Sarcoplasmic Signaling; Techniques; Transport; Ventricular; %N 5 %P 543--550 %R 10.1161/01.RES.0000158966.58380.37 %T Alterations in early action potential repolarization causes localized failure of sarcoplasmic reticulum Ca$^2+$ release. %U http://dx.doi.org/10.1161/01.RES.0000158966.58380.37 %V 96 %X Depressed contractility of failing myocytes involves a decreased rate of rise of the Ca$^2+$ transient. Synchronization of Ca$^2+$ release from the junctional sarcoplasmic reticulum (SR) is responsible for the rapid rise of the normal Ca$^2+$ transient. This study examined the idea that spatially and temporally dyssynchronous SR Ca$^2+$ release slows the rise of the cytosolic Ca$^2+$ transient in failing feline myocytes. Left ventricular hypertrophy (LVH) with and without heart failure (HF) was induced in felines by constricting the ascending aorta. Ca$^2+$ transients were measured in ventricular myocytes using confocal line scan imaging. Ca$^2+$ transients were induced by field stimulation, square wave voltage steps, or action potential (AP) voltage clamp. SR Ca$^2+$ release was significantly less well spatially and temporally synchronized in field-stimulated HF versus control or LVH myocytes. Surprisingly, depolarization of HF cells to potentials where Ca$^2+$ currents (ICa) were maximal resynchronized SR Ca$^2+$ release. Correspondingly, decreases in the amplitude of ICa desynchronized SR Ca$^2+$ release in control, LVH, and HF myocytes to the same extent. HF myocytes had significant loss of phase 1 AP repolarization and smaller ICa density, which should both reduce Ca$^2+$ influx. When normal myocytes were voltage clamped with HF AP profiles SR Ca$^2+$ release was desynchronized. SR Ca$^2+$ release becomes dyssynchronized in failing feline ventricular myocytes because of reductions in Ca$^2+$ influx induced in part by alterations in early repolarization of the AP. Therefore, therapies that restore normal early repolarization should improve the contractility of the failing heart.

@article{Harr_2005_543, abstract = {Depressed contractility of failing myocytes involves a decreased rate of rise of the {C}a$^{2+}$ transient. Synchronization of {C}a$^{2+}$ release from the junctional sarcoplasmic reticulum (SR) is responsible for the rapid rise of the normal {C}a$^{2+}$ transient. This study examined the idea that spatially and temporally dyssynchronous SR {C}a$^{2+}$ release slows the rise of the cytosolic {C}a$^{2+}$ transient in failing feline myocytes. Left ventricular hypertrophy (LVH) with and without heart failure (HF) was induced in felines by constricting the ascending aorta. {C}a$^{2+}$ transients were measured in ventricular myocytes using confocal line scan imaging. {C}a$^{2+}$ transients were induced by field stimulation, square wave voltage steps, or action potential (AP) voltage clamp. SR {C}a$^{2+}$ release was significantly less well spatially and temporally synchronized in field-stimulated HF versus control or LVH myocytes. Surprisingly, depolarization of HF cells to potentials where {C}a$^{2+}$ currents (ICa) were maximal resynchronized SR {C}a$^{2+}$ release. Correspondingly, decreases in the amplitude of ICa desynchronized SR {C}a$^{2+}$ release in control, LVH, and HF myocytes to the same extent. HF myocytes had significant loss of phase 1 AP repolarization and smaller ICa density, which should both reduce {C}a$^{2+}$ influx. When normal myocytes were voltage clamped with HF AP profiles SR {C}a$^{2+}$ release was desynchronized. SR {C}a$^{2+}$ release becomes dyssynchronized in failing feline ventricular myocytes because of reductions in {C}a$^{2+}$ influx induced in part by alterations in early repolarization of the AP. Therefore, therapies that restore normal early repolarization should improve the contractility of the failing heart.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Harris, David M and Mills, Geoffrey D and Chen, Xiongwen and Kubo, Hajime and Berretta, Remus M and Votaw, V. Scott and Santana, Luis F and Houser, Steven R}, biburl = {https://www.bibsonomy.org/bibtex/2420604d778cf3ff54a877abc2fa58811/hake}, description = {The whole bibliography file I use.}, doi = {10.1161/01.RES.0000158966.58380.37}, file = {Harr_2005_543.pdf:Harr_2005_543.pdf:PDF}, interhash = {4933a848496289f47d2d124b242545e7}, intrahash = {420604d778cf3ff54a877abc2fa58811}, journal = {Circ. Res.}, keywords = {Action Animals; Aortic Calcium Calcium; Cardiac; Cats; Congestive; Constriction, Contraction; Diseases; Failure, Heart Hypertrophy, Ion Left Myocardial Myocytes, Patch-Clamp Pathologic; Potentials; Reticulum Sarcoplasmic Signaling; Techniques; Transport; Ventricular;}, month = Mar, number = 5, pages = {543--550}, pii = {01.RES.0000158966.58380.37}, pmid = {15705962}, timestamp = {2009-06-03T11:21:13.000+0200}, title = {Alterations in early action potential repolarization causes localized failure of sarcoplasmic reticulum {C}a$^{2+}$ release.}, url = {http://dx.doi.org/10.1161/01.RES.0000158966.58380.37}, volume = 96, year = 2005 }