Regional expression of phospholamban in the human heart

Background: Several independent lines of evidence indicate that phospholamb an (PLB) expression correlates positively with depression of force of contr action and duration of contraction in isolated cardiac preparations of seve ral animal species. Here, we studied whether PLB levels correlate with atte nuation of contractility and enhancement of contractile time parameters in different parts of the human heart. Methods: Force of contraction was measu red in isolated electrically driven atrial and ventricular preparations fro m human hearts. Ca2+-uptake by human atrial and ventricular homogenates was assayed at different ionized Ca2+-concentrations. Protein expression of PL B and the sarcoplasmic Ca2+-ATPase (SERCA) was measured in homogenates by q uantitative immunoblotting using specific antibodies. PLB mRNA expression w as quantified in human cardiac preparations by Northern blot analysis. Resu lts: The duration of contraction in isolated preparations of human right ve ntricle (RV) was double that found in right atrial preparations (RA) (620+/ -25 ms versus 308+/-15 ms). In RA, PLB expression was reduced by 44% at the protein level and by 34% at the mRNA level compared to RV. In contrast, th e SERCA protein content was increased by 104% in RA compared to RV. Ca2+-up take at low ionized Ca2+-concentration, where the inhibiting effect of PLB is maximal, amounted to 1.39+/-0.28 nmol Ca2+/mg protein in RA and to 0.62/-0.09 nmol Ca2+/mg protein in RV (n=6 both). Conclusions: It is suggested that duration of contraction is shorter in human atrium versus ventricle du e to the combined effect of decreased PLB levels (which inhibits SERCA func tion) and increased SERCA levels. The lower relative ratio of PLB to SERCA leads to less inhibition of SERCA and increased Ca2+-uptake which enhances relaxation and contraction in human atrium. (C) 1999 Elsevier Science B.V. All rights reserved.