Calcium buffering in the heart in health and disease

Changes of intracellular Ca2+ concentration regulate many aspects of cardiac myocyte function. About 99% of the cytoplasmic calcium in cardiac myocytes is bound to buffers, and their properties will therefore have a major influence on Ca2+ signaling. This article considers the fundamental properties and identities of the buffers and how to measure them. It reviews the effects of buffering on the systolic Ca2+ transient and how this may change physiologically, and in heart failure and both atrial and ventricular arrhythmias, as well. It is concluded that the consequences of this strong buffering may be more significant than currently appreciated, and a fuller understanding is needed for proper understanding of cardiac calcium cycling and contractility

Functional and structural insights into Sarcolipin, a regulator of the Sarco-endoplasmic reticulum Ca2+-ATPases

International audienceSarcolipin (SLN), a transmembrane peptide from sarcoplasmic reticulum, is one of the major proteins involved in the muscle contraction/relaxation process. A number of enzymological studies have underlined its regulatory role in connection with the SERCA1a activity. Indeed, SLN folds as a unique transmembrane helix and binds to SERCA1a in a groove close to transmembrane helices M2, M6, and M9, as proposed initially by cross-linking experiments and recently detailed in the 3D structures of the SLN–Ca2+-ATPase complex. In addition, association of SLN with SERCAs may depend on its phosphorylation. SLN possesses a peculiar C-terminus (RSYQY) critical for the regulation of the ATPases. This luminal tail appears to be essential for addressing SLN to the ER membrane. Moreover, we recently demonstrated that some SLN isoforms are acylated on cysteine 9, a feature which remained unnoticed so far even in the recent crystal structures of the SLN–SERCA1a complex. The removal of the fatty acid chain was shown to increase the activity of the membrane-embedded Ca2+-ATPase by about 20 %. The exact functional and structural role of this post-translational modification is presently unknown. Recent data are in favor of a key regulator role of SLN in muscle-based thermogenesis in mammals. The possible link of SLN to heat production could occur through an uncoupling of the SERCA1a-mediated ATP hydrolysis from calcium transport. Considering those particular features and the fact that SLN is not expressed at the same level in different tissues, the role of SLN and its exact mechanism of regulation remain sources of interrogation