Cardiac myocytes Ca2+ and Na+ regulation in normal and failing hearts.
Ca(2+) is a central player in the excitation-contraction coupling of cardiac myocytes, the process that enables the heart to contract and relax. Mishandling of Ca(2+) is a central cause of both contractile dysfunction and arrhythmias in pathophysiological conditions such as heart failure (HF). Upon electrical excitation, Ca(2+) enters the myocytes via voltage-gated Ca(2+) channels and induces further Ca(2+) release from the sarcoplasmic reticulum (SR). This raises the free intracellular Ca(2+) concentration ([Ca(2+)](i)), activating contraction. Relaxation is driven by [Ca(2+)](i) decline, mainly due to re-uptake into the SR via SR Ca(2+)-ATPase and extrusion via the sarcolemmal Na(+)/Ca(2+) 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 [Ca(2+)]. [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 Na(+) 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 Ca(2+) and Na(+) in myocytes from normal and failing hearts.
Bers
Donald M
DM
Department of Physiology, Loyola University Chicago, Stritch School of Medicine, Maywood, IL 60153, USA. dbers@lumc.edu
Despa
Sanda
S
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology*; D008954:Models, Biological; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000502:physiology*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000502:physiology*
D019831:Sodium-Calcium Exchanger; D012964:Sodium; D002118:Calcium