Cardiac myocytes Ca2+ and Na+ regulation in normal and failing hearts

Donald M. Bers, Sanda Despa

Research output: Contribution to journalReview articlepeer-review

148 Scopus citations


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.

Original languageEnglish
Pages (from-to)315-322
Number of pages8
JournalJournal of Pharmacological Sciences
Issue number5
StatePublished - 2006

Bibliographical note

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  • Heart failure
  • Na/Ca exchange
  • Na/K pump
  • Phospholemman
  • Sarcoplasmic reticulum Ca content

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology


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