Phosphorylation and other conundrums of Na/Ca exchanger, NCX1

Abdul M. Ruknudin*, Shao Kui Wei, Mark C. Haigney, W. J. Lederer, Dan H. Schulze

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

17 Scopus citations


The Na+/Ca2+ exchanger (NCX) is an important Ca 2+ transport mechanism in virtually all cells in the body. There are three genes that control the expression of NCX in mammals. There are at least 16 alternatively spliced isoforms of NCX1 that target muscle and nerve and other tissues. Here we briefly discuss three remarkable regulatory issues or "conundrums" that involve the most prevalently expressed gene, NCX1. (1) How is NCX1 regulated by phosphorylation? We suggest that the macromolecular complex of NCX1 plays a critical role in the regulation of NCX. The role of the macromolecular complex and evidence supporting its existence and functional importance is presented. (2) Can there be transport block of a single "mode" of NCX1 transport by drugs or therapeutic agents? The simple answer is "no."Abrief explanation is provided. (3) How can NCX1 knockout mice live? The answer is "by other compensatory regulatory mechanisms." These conundrums highlight important features in NCX1 and lay the foundation for new experiments to elucidate function and regulation of NCX1 and provide a context for investigations that seek to understand novel therapeutic agents.

Original languageEnglish
Title of host publicationSodium-Calcium Exchange and the Plasma Membrane Ca2+ATPase in Ce;; Funcyion
Subtitle of host publicationFifth International Conference
PublisherBlackwell Publishing Inc.
Number of pages16
ISBN (Print)1573316490, 9781573316491
StatePublished - Mar 2007
Externally publishedYes

Publication series

NameAnnals of the New York Academy of Sciences
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632


  • Modespecific inhibition
  • NCX macromolecular complex
  • NCX1 knockout
  • Protein kinase A
  • Regulation
  • β-adrenergic stimulation


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