Ca2+ is a central player in the excitation-contraction coupling of cardiac myocytes, the process that enables the heart to contract and relax. Mishandling of Ca2+ is a central cause of both contractile dysfunction and arrhythmias in pathophysiological conditions such as heart failure (HF). Upon electrical excitation, Ca2+ enters the myocytes via voltage-gated Ca2+ channels and induces further Ca2+ release from the sarcoplasmic reticulum (SR). This raises the free intracellular Ca2+ concentration ([Ca2+]i), activating contraction. Relaxation is driven by [Ca2+]i decline, mainly due to re-uptake into the SR via SR Ca2+-ATPase and extrusion via the sarcolemmal Na+/Ca2+ exchange, NCX. Intracellular Na+ concentration ([Na+]i) is a main regulator of NCX, and thus [Na+]i plays an important role in controlling the cytosolic and SR [Ca2+]. [Na+]i may have an even more important role in HF because NCX is generally upregulated. There are several pathways for Na+ entry into the cells, whereas the Na+/K+ pump (NKA) is the main Na2+ extrusion pathway and therefore is essential in maintaining the transmembrane Na+ gradient. Phospholemman is an important regulator of NKA function (decreasing [Na+]i affinity unless it is phosphorylated). Here we discuss the interplay between Ca2+ and Na+ in myocytes from normal and failing hearts.
- Heart failure
- Na/Ca exchange
- Na/K pump
- Sarcoplasmic reticulum Ca content
ASJC Scopus subject areas