TY - JOUR
T1 - Lithium-calcium exchange is mediated by a distinct potassium-independent sodium-calcium exchanger
AU - Palty, Raz
AU - Ohana, Ehud
AU - Hershfinkel, Michal
AU - Volokita, Micha
AU - Elgazar, Vered
AU - Beharier, Ofer
AU - Silverman, William F.
AU - Argaman, Miriam
AU - Sekler, Israel
PY - 2004/6/11
Y1 - 2004/6/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=2942623673&partnerID=8YFLogxK
U2 - 10.1074/jbc.M401229200
DO - 10.1074/jbc.M401229200
M3 - Article
AN - SCOPUS:2942623673
SN - 0021-9258
VL - 279
SP - 25234
EP - 25240
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 24
ER -