Cardiac Myocytes Ca2+ and Na+ Regulation in Normal and Failing Hearts

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 elec...

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Bibliographic Details
Published in:Journal of Pharmacological Sciences 2006, Vol.100(5), pp.315-322
Main Authors: Bers, Donald M., Despa, Sanda
Format: Article
Language:English
Subjects:
Animals
Calcium - metabolism
heart failure
Heart Failure - metabolism
Heart Failure - physiopathology
Models, Biological
Myocardial Contraction
Myocytes, Cardiac - metabolism
Myocytes, Cardiac - physiology
Na+/Ca2+ exchange
Na+/K+ pump
phospholemman
Sarcoplasmic Reticulum - metabolism
sarcoplasmic reticulum Ca2+ content
Sodium - metabolism
Sodium-Calcium Exchanger - physiology
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Summary: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 up-regulated. 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 Ca2+ and Na+ in myocytes from normal and failing hearts.
ISSN:1347-8613
1347-8648
DOI:10.1254/jphs.CPJ06001X