Lithium-calcium exchange is mediated by a distinct potassium-independent sodium-calcium exchanger

Raz Palty, Ehud Ohana, Michal Hershfinkel, Micha Volokita, Vered Elgazar, Ofer Beharier, William F. Silverman, Miriam Argaman, Israel Sekler

Research output: Contribution to journalArticlepeer-review

108 Scopus citations

Abstract

Sodium-calcium exchangers have long been considered inert with respect to monovalent cations such as lithium, choline, and N-methyl-D-glucamine. A key question that has remained unsolved is how despite this, Li+ catalyzes calcium exchange in mammalian tissues. Here we report that a Na +/Ca2+ exchanger, NCLX cloned from human cells (known as FLJ22233), is distinct from both known forms of the exchanger, NCX and NCKX in structure and kinetics. Surprisingly, NCLX catalyzes active Li +/Ca2+ exchange, thereby explaining the exchange of these ions in mammalian tissues. The NCLX protein, detected as both 70- and 55-KDa polypeptides, is highly expressed in rat pancreas, skeletal muscle, and stomach. We demonstrate, moreover, that NCLX is a K+-/independent exchanger that catalyzes Ca2+ flux at a rate comparable with NCX1 but without promoting Na+/Ba2+ exchange. The activity of NCLX is strongly inhibited by zinc, although it does not transport this cation. NCLX activity is only partially inhibited by the NCX inhibitor, KB-R7943. Our results provide a cogent explanation for a fundamental question. How can Li + promote Ca2+ exchange whereas the known exchangers are inert to Li+ ions? Identification of this novel member of the Na +/Ca2+ superfamily, with distinct characteristics, including the ability to transport Li+, may provide an explanation for this phenomenon.

Original languageEnglish
Pages (from-to)25234-25240
Number of pages7
JournalJournal of Biological Chemistry
Volume279
Issue number24
DOIs
StatePublished - 11 Jun 2004

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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