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Selected Publication:
Antoons, G; Ver Heyen, M; Raeymaekers, L; Vangheluwe, P; Wuytack, F; Sipido, KR.
Ca2+ uptake by the sarcoplasmic reticulum in ventricular myocytes of the SERCA2b/b mouse is impaired at higher Ca2+ loads only.
Circ Res. 2003; 92(8):881-887
Doi: 10.1161/01.RES.0000069032.81501.98
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- Leading authors Med Uni Graz
- Antoons Gudrun
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Blotting, Western -
- Calcium - metabolism Calcium - pharmacokinetics
- Calcium-Transporting ATPases - genetics Calcium-Transporting ATPases - metabolism
- Genotype -
- Heart Ventricles - cytology Heart Ventricles - metabolism
- Isoenzymes - genetics Isoenzymes - metabolism
- Membrane Potentials - physiology
- Mice -
- Mice, Knockout -
- Mutation -
- Myocytes, Cardiac - cytology Myocytes, Cardiac - metabolism
- Sarcoplasmic Reticulum - metabolism
- Sarcoplasmic Reticulum Calcium-Transporting ATPases -
- Sodium-Calcium Exchanger - metabolism
- Find related publications in this database (Keywords)
- ventricular myocytes
- transgenic mice
- sarcoplasmic reticulum Ca(2+)-ATPase
- excitation-contraction coupling
- Na(+)-Ca2(+) exchange