Abstract
See article by Terracciano et al. [2] (pages 38–47) in this issue. The failing human ventricle suffers from two major problems: (1) During diastole, relaxation is retarded and remains eventually incomplete. (2) During systole, the force-frequency relation is blunted, i.e. an increase from 60 to 120 beats-per-min does not increase the contractile force as it is typical in non-failing tissue. Both problems have been linked to reduced expression and function of sarcoplasmic reticulum (SR) Ca2+ ATPase (SERCA) proteins. Studies in isolated human ventricular trabeculae [1] have shown that incomplete Ca2+ reuptake by SERCA can cause (1) a diastolic accumulation of Ca2+ ions in the cytosol which impairs diastolic relaxation, and (2) a reduction of releasable SR Ca2+ with the consequence of a reduced systolic Ca2+ activation of force and a blunted force-frequency relation. Since failing human myocardium was shown to overexpress the Na+/Ca2+-exchanger (mRNA and protein [1]), enhanced Ca2+ efflux by Na+/Ca2+-exchange has been suggested to partially compensate impaired diastolic Ca2+ removal. The paper of Terracciano et al. ([2] in this issue) confirms this view. In addition, it introduces a new idea: the enhanced expression and function of the Na+/Ca2+-exchanger may facilitate Ca2+ reuptake by SERCA and thereby compensate for the impaired SR Ca2+ load. Terraciano et al. [2,3] compared protein concentrations and functions between ventricular myocytes from transgenic mice (TR) that overexpress the Na+/Ca2+-exchanger and non-transgenic (non-TR) wild-type littermates. They find that the protein levels of the Na+/Ca2+-exchanger are approximately 2.4-fold elevated [3,4]) whilst the concentrations of other Ca2+ handling proteins such as SERCA, calsequestrin and phospholambam were not different. With this background, the authors can evaluate the consequences … * Tel.: +49-345-557-1886; fax: +49-345-557-4019 gerrit.isenberg{at}medizin.uni-halle.de
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
