Abstract
Adult SERCA2(b/b) mice expressing the non-muscle Ca2+ transport ATPase
isoform SERCA2b in the heart instead of the normally predominant
sarcomeric SERCA2a isoform, develop mild concentric ventricular hypertrophy
with impaired cardiac contractility and relaxation Circ. Res. 89
(2001) 838. Results from a separate study on transgenic mice overexpressing
SERCA2b in the normal SERCA2a context were interpreted to show that
SERCA2b and SERCA2a are differentially targeted within the cardiac
sarcoplasmic reticulum (SR) J. Biol. Chem. 275 (2000) 24722. Since
a different subcellular distribution of SERCA2b could underlie alterations
in Ca2+ handling observed in SERCA2(b/b), we wanted to compare SERCA2b
distribution in SERCA2(b/b) with that of SERCA2a in wild-type (WT).
Using confocal microscopy on immunostained fixed myocytes and BODIPY-thapsigargin-stained
living cells, we found that in SERCA2(b/b) mice SERCA2b is correctly
targeted to cardiac SR and is present in the same SR regions as SERCA2a
and SERCA2b in WT. We conclude that there is no differential targeting
of SERCA2a and SERCA2b since both are found in the longitudinal SR
and in the SR proximal to the Z-bands. Therefore, alterations in
Ca2+ handling and the development of hypertrophy in adult SERCA2(b/b)
mice do not result from different SERCA2b targeting.
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