Abstract 14031: Selective Modulation of SERCA Did Not Affect Ca2+ Leak from Sarcoplasmic Reticulum in Transgenic Mouse Models
Introduction: Intracellular Ca2+ concentration ([Ca2+]i) is an important determinant of cardiac contractility and sarcoplasmic reticulum (SR) has a central role to manipulate [Ca2+]i. Two important regulators of the Ca2+ content of SR are the activity of Ca2+ pump (SERCA) and the Ca2+ leak through ryanodine receptor (RyR). Ca2+ release from SR is known to have a steep relation to the Ca2+ content. The role of two regulatory mechanisms (SERCA activity and Ca2+ leak) is very important, however, the direct relationship between SERCA activity and Ca2+ leak has not been investigated.
Methods: We used two transgenic mouse models of either increase (overexpression of SERCA) (SERCA-TG) or decrease (overexpression of negative regulator of SERCA, sarcolipin) (SLN-TG) the SERCA activity selectively. Non-transgenic littermates are used as control (NTG). Ca2+ transient (CaT) was measured in isolated papillary muscles using the aequorin method. Ca2+ uptake and Ca2+ leak of SR are estimated using saponin skinned ventricular trabeculae.
Results: In SERCA-TG, the peak of CaT increased and the time course of CaT was accelerated. In this condition, Ca2+ uptake of the SR was significantly increased (99.0% increases at pCa6.6). However, Ca2+ leak from SR did not change significantly. In SLN-TG, the peak of CaT decreased and the time course of CaT was slowed, and Ca2+ uptake of the SR was significantly decreased (31.2% decreases at pCa6.6). Ca2+ leak from SR did not change significantly again.
Conclusion: Selective modulation of SERCA effectively modulates Ca2+ uptake and content of SR without changes in Ca2+ leak from SR.
- © 2012 by American Heart Association, Inc.