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Title: Ca2+ uptake by the sarcoplasmic reticulum in ventricular myocytes of the SERCA2b/b mouse is impaired at higher Ca2+ loads only
Authors: Antoons, Gudrun ×
Ver Heyen, Mark
Raeymaekers, Luc
Vangheluwe, Peter
Wuytack, Frank
Sipido, Karin #
Issue Date: May-2003
Publisher: Lippincott Williams & Wilkins
Series Title: Circulation Research vol:92 issue:8 pages:881-7
Abstract: SERCA2a is the cardiac-specific isoform of Ca2+-ATPase of the sarcoplasmic reticulum (SR). A reduction of SERCA2a has been implicated in the contractile dysfunction of heart failure, and partial knockout of the SERCA2 gene (Atp2a2+/- mice) reiterated many of the features of heart failure. Yet, mice with a mutation of Atp2a2, resulting in full suppression of the SERCA2a isoform and expression of the SERCA2b isoform only (SERCA2b/b), showed only moderate functional impairment, despite a reduction by 40% of the SERCA2 protein levels. We examined in more detail the Ca2+ handling in isolated cardiac myocytes from SERCA2b/b. At 0.25 Hz stimulation, the amplitude of the [Ca2+]i transients, SR Ca2+ content, diastolic [Ca2+]i, and density of ICaL were comparable between WT and SERCA2b/b. However, the decline of [Ca2+]i was slower (t1/2 154+/-7 versus 131+/-5 ms; P<0.05). Reducing the amplitude of the [Ca2+]i transient (eg, SR depletion), removed the differences in [Ca2+]i decline. In contrast, increasing the Ca2+ load revealed pronounced reduction of SR Ca2+ uptake at high [Ca2+]i. There was no increase in Na+-Ca2+ exchange protein or function. Theoretical modeling indicated that in the SERCA2b/b mouse, the higher Ca2+ affinity of SERCA2b partially compensates for the 40% reduction of SERCA expression. The lack of SR depletion in the SERCA2b/b may also be related to the absence of upregulation of Na+-Ca2+ exchange. We conclude that for SERCA isoforms with increased affinity for Ca2+, a reduced expression level is better tolerated as Ca2+ uptake and storage are impaired only at higher Ca2+ loads.
URI: 
ISSN: 0009-7330
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Physiology Section (-)
Cardiology
Experimental Cardiology
Laboratory of Cellular Transport Systems
× corresponding author
# (joint) last author

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