Influence of transgenic overexpression of phospholamban on postextrasystolic potentiation.
Twelve mice with PLB overexpression (PLBOE), and 11 isogenic FVB/N wild-type (WT) controls, were anesthetized and instrumented with a 1.4 F Millar catheter in the LV and a 1 F pacemaker in the right atrium. At a cycle length of 200 ms and a fixed extrastimulus of 120 ms, extrastimuli with increasing intervals (PESI) up to 1000 ms were introduced, and the peak rates of LV isovolumic contraction (+/- dP/dtmax) were normalized and fit to monoexponential equations. In a subset of animals, the protocols were repeated after ryanodine (4 ng/g) was given to deplete SR Ca2+ stores. The time constant and the plateau of the exponential curve fits were significantly greater in PLBOE than WT (107.8 +/- 7.0 v 75.2 +/- 5.5 ms and 1.39 +/- 0.03 v 1.08 +/- 0.02, both P < 0.05). At 200, 600 and 1000 ms, the normalized dP/dt was significantly greater in PLBOE than WT. After ryanodine, normalized dP/dt was significantly decreased in PLBOE, but unchanged in WT. The protein levels of the sodium-calcium exchanger normalized to calsequestrin were increased 3.7 +/- 0.3-fold in PLBOE compared to controls. In conclusion, the phospholamban level is a critical determinant of postextrasystolic potentiation in this transgenic model, and is differentially impaired by ryanodine at long diastolic intervals in PLBOE v controls. These differences may be due in part to changes in the protein level and resultant activity of the sodium calcium exchanger.
Hoit
B D
BD
Division of Cardiology, University of Cincinnati Medical Center, OH 45267-0542, USA.
Tramuta
D A
DA
Kadambi
V J
VJ
Dash
R
R
Ball
N
N
Kranias
E G
EG
Walsh
R A
RA
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D002135:Calcium-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005117:Cardiac Complexes, Premature / Q000235:genetics / Q000503:physiopathology*; D003971:Diastole; D004558:Electric Stimulation; D004562:Electrocardiography; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D006439:Hemodynamics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012433:Ryanodine / Q000494:pharmacology; D013599:Systole; D016277:Ventricular Function, Left; D000099211:Phospholamban
D000251:Adenosine Triphosphatases; D002135:Calcium-Binding Proteins; D012433:Ryanodine; D000099211:Phospholamban