Overexpression of SERCA2b in transgenic mice increased the apparent pump affinity for Ca(2+) (0.199 vs 0.269 micrometer, p < 0.01) and increased cardiac contractility compared with wild-type mice.
Does overexpression of SERCA2b improve sarcoplasmic reticulum calcium transport function and cardiac contractility in mice?
Overexpression of SERCA2b in the heart increases sarcoplasmic reticulum calcium transport function and cardiac contractility, suggesting a specialized role in regulating beat-to-beat contraction.
Absolute Event Rate: 0.199% vs 0.269%
p-value: p=< 0.01
The sarcoplasmic reticulum calcium ATPase SERCA2b is an alternate isoform encoded by the SERCA2 gene. SERCA2b is expressed ubiquitously and has a higher Ca(2+) affinity compared with SERCA2a. We made transgenic mice that overexpress the rat SERCA2b cDNA in the heart. SERCA2b mRNA level was approximately approximately 20-fold higher than endogenous SERCA2b mRNA in transgenic hearts. SERCA2b protein was increased 8-10-fold in the heart, whereas SERCA2a mRNA/protein level remained unchanged. Confocal microscopy showed that SERCA2b is localized preferentially around the T-tubules of the SR, whereas SERCA2a isoform is distributed both transversely and longitudinally in the SR membrane. Calcium-dependent calcium uptake measurements showed that the maximal velocity of Ca(2+) uptake was not changed, but the apparent pump affinity for Ca(2+) (K(0.5)) was increased in SERCA2b transgenic mice (0.199 +/- 0.011 micrometer) compared with wild-type control mice (0.269 +/- 0.012 micrometer, p < 0.01). Work-performing heart preparations showed that SERCA2b transgenic hearts had a higher rates of contraction and relaxation, shorter time to peak pressure and half-time for relaxation than wild-type hearts. These data show that SERCA2b is associated in a subcompartment within the sarcoplasmic reticulum of cardiac myocytes. Overexpression of SERCA2b leads to an increase in SR calcium transport function and increased cardiac contractility, suggesting that SERCA2b plays a highly specialized role in regulating the beat-to-beat contraction of the heart.
Greene et al. (2000) studied this question. Overexpression of SERCA2b vs. Wild-type control mice was evaluated on Apparent pump affinity for Ca(2+) (K(0.5)) in micrometers (p=< 0.01). Overexpression of SERCA2b in transgenic mice increased the apparent pump affinity for Ca(2+) (0.199 vs 0.269 micrometer, p < 0.01) and increased cardiac contractility compared with wild-type mice.