A novel molecular determinant for cAMP-dependent regulation of the frog heart Na+-Ca2+ exchanger

Yaroslav M. Shuba, Tomoko Iwata, Valery G. Naidenov, Murat Oz, Katherine Sandberg, Alexander Kraev, Ernesto Carafoli, Martin Morad

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)


Na+-Ca2+ exchanger is one of the major sarcolemmal Ca2+ transporters of cardiac myocytes. In frog ventricular myocytes the exchanger is regulated by isoproterenol via a β-adrenoreceptor/adenylate- cyclase/cAMP-dependent signaling pathway providing a molecular mechanism for the relaxant effect of the hormone. Here, we report on the presence of a novel exon of 27-base pair insertion, which generates a nucleotide binding motif (P-loop) in the frog cardiac Na+-Ca2+ exchanger. To examine the functional role of this motif, we constructed a full-length frog heart Na+- Ca2+ exchanger cDNA (fNCX1a) containing this exon. The functional expression of fNCX1a in oocytes showed characteristic voltage dependence, divalent (Ni2+, Cd2+) inhibition, and sensitivity to cAMP in a manner similar to that of native exchanger in frog myocytes. In oocytes expressing the dog heart NCX1 or the frog mutant (ΔfNCX1a) lacking the 9-amino acid exon, cAMP failed to regulate Na+-dependent Ca2+ uptake. We suggest that this motif is responsible for the observed cAMP-dependent functional differences between the frog and the mammalian hearts.

Original languageEnglish
Pages (from-to)18819-18825
Number of pages7
JournalJournal of Biological Chemistry
Issue number30
Publication statusPublished - Jul 24 1998
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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