How can overexpression of Na(+),Ca(2+)-exchanger compensate the negative inotropic effects of downregulated SERCA?

Terraciano et al. [2,3] compared protein concentrations and functions between ventricular myocytes from trans1 21 1 21 1. Importance of the Na /Ca -exchanger for the genic mice (TR) that overexpress the Na /Ca -ex21 Ca distribution in the failing human heart changer and non-transgenic (non-TR) wild-type littermates. 1 21 They find that the protein levels of the Na /Ca -exThe failing human ventricle suffers from two major changer are approximately 2.4-fold elevated [3,4]) whilst 21 problems: (1) During diastole, relaxation is retarded and the concentrations of other Ca handling proteins such as remains eventually incomplete. (2) During systole, the SERCA, calsequestrin and phospholambam were not difforce-frequency relation is blunted, i.e. an increase from 60 ferent. With this background, the authors can evaluate the to 120 beats-per-min does not increase the contractile force consequences of the overexpression of a single protein 21 1 21 as it is typical in non-failing tissue. Both problems have species for the Ca fluxes mediated by Na /Ca -exbeen linked to reduced expression and function of sarcochange. 21 plasmic reticulum (SR) Ca ATPase (SERCA) proteins. Studies in isolated human ventricular trabeculae [1] have 21 21 shown that incomplete Ca reuptake by SERCA can 3. The balance of Ca fluxes 21 cause (1) a diastolic accumulation of Ca ions in the