Regulation of Ca2+ and Na+ in normal and failing cardiac myocytes

Research output: Chapter in Book/Report/Conference proceedingConference contribution

109 Citations (Scopus)

Abstract

Ca2+ in cardiac myocytes regulates contractility and relaxation, and Ca2+ and Na +regulation are linked via Na +/Ca2+ exchange (NCX). Heart failure (HF) is accompanied by contractile dysfunction and arrhythmias, both of which may be due to altered cellular Ca2+ handling. Smaller Ca2+ transient and sarcoplasmic reticulum (SR) Ca2+ content cause systolic dysfunction in HF. The reduced SR Ca2+ content is due to: (a) reduced SR Ca 2+-ATPase function (which also contributes to diastolic dysfunction), (b) increased expression and function of NCX (which competes with SR Ca 2+-ATPase during relaxation, but preserves diastolic function), and (c) enhanced diastolic SR Ca2+ leak. Relative contributions of these may vary with HF etiology and stage. Triggered arrhythmias (e.g., delayed afterdepolarizations [DADs]) are prominent in HF. DADs are due to spontaneous SR Ca2+ release and consequent activation of transient inward NCX current, which in HF allows DADs to more readily trigger arrhythmogenic action potentials. Thus NCX and Na+ are critical in systolic and diastolic function and arrhythmias. [Na+]i is elevated in HF, which may limit SR unloading and provide some Ca2+ influx during the HF action potential, thus limiting the depression of systolic function. High [Na+]i in HF is due to enhanced Na+ influx. Cellular Na+/K+-ATPase (NKA) function appears unaltered, despite reduced NKA expression. This dichotomy led us to test NKA regulation by phospholemman (PLM). We find that PLM regulates NKA in a manner analogous to phospholamban regulation of SR Ca2+-ATPase (i.e., inhibition that is relieved by PLM phosphorylation). We measured intermolecular FRET between PLM and NKA, which is reduced upon PLM phosphorylation. The lower expression level of more phosphorylated PLM in HF may explain the above dichotomy. Thus, altered Ca2+ and Na+ handling contributes to altered contractile function and arrhythmogenesis in HF.

Original languageEnglish (US)
Title of host publicationAnnals of the New York Academy of Sciences
Pages165-177
Number of pages13
Volume1080
DOIs
StatePublished - Oct 2006
Externally publishedYes

Publication series

NameAnnals of the New York Academy of Sciences
Volume1080
ISSN (Print)00778923
ISSN (Electronic)17496632

Fingerprint

Cardiac Myocytes
Heart Failure
Sarcoplasmic Reticulum
Adenosine Triphosphatases
Sarcoplasmic Reticulum Calcium-Transporting ATPases
Cardiac Arrhythmias
Phosphorylation
Action Potentials
Calcium-Transporting ATPases
Unloading
phospholemman
Chemical activation
sodium-translocating ATPase

Keywords

  • Calcium
  • Heart failure
  • Na-Ca exchange
  • Na/K-ATPase
  • Phospholemman
  • SR Ca -ATPase

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Bers, D. M., Despa, S., & Bossuyt, J. B. C. (2006). Regulation of Ca2+ and Na+ in normal and failing cardiac myocytes. In Annals of the New York Academy of Sciences (Vol. 1080, pp. 165-177). (Annals of the New York Academy of Sciences; Vol. 1080). https://doi.org/10.1196/annals.1380.015

Regulation of Ca2+ and Na+ in normal and failing cardiac myocytes. / Bers, Donald M; Despa, Sanda; Bossuyt, Julie B C.

Annals of the New York Academy of Sciences. Vol. 1080 2006. p. 165-177 (Annals of the New York Academy of Sciences; Vol. 1080).

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Bers, DM, Despa, S & Bossuyt, JBC 2006, Regulation of Ca2+ and Na+ in normal and failing cardiac myocytes. in Annals of the New York Academy of Sciences. vol. 1080, Annals of the New York Academy of Sciences, vol. 1080, pp. 165-177. https://doi.org/10.1196/annals.1380.015
Bers DM, Despa S, Bossuyt JBC. Regulation of Ca2+ and Na+ in normal and failing cardiac myocytes. In Annals of the New York Academy of Sciences. Vol. 1080. 2006. p. 165-177. (Annals of the New York Academy of Sciences). https://doi.org/10.1196/annals.1380.015
Bers, Donald M ; Despa, Sanda ; Bossuyt, Julie B C. / Regulation of Ca2+ and Na+ in normal and failing cardiac myocytes. Annals of the New York Academy of Sciences. Vol. 1080 2006. pp. 165-177 (Annals of the New York Academy of Sciences).
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