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.
View details for Web of Science ID 000083749100006
View details for PubMedID 10591027