Influence of transgenic overexpression of phospholamban on postextrasystolic potentiation

Twelve mice with PLB overexpression (PLBOE), and 11 isogenic FVB/N wild-typ e (WT) controls, were anesthetized and instrumented with a 1.4 F Millar cat heter 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 i sovolumic contraction (+/-dP/dt(max)) were normalized and fit to monoexpone ntial 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 a nd 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 sign ificantly greater in PLBOE than WT, After ryanodine, normalized dP/dt was s ignificantly 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 phospholam ban level is a critical determinant of postextrasystolic potentiation in th is transgenic model, and is differentially impaired by ryanodine at long di astolic intervals in PLBOE v controls. These differences may be due in part to changes in the protein level and resultant activity of the sodium calci um exchanger. (C) 1999 Academic Press.