K+-dependent Na+/Ca2+ exchangers in the brain.
Sodium-calcium exchange was first characterized in heart myocytes and squid axon more than 3 decades ago. Since then, it has been appreciated that functioning of the Na/Ca exchanger molecule plays a critical role in calcium homeostasis in neurons. Genome analysis indicates that Na/Ca exchangers are a superfamily encoded by 7 different genes divided into 2 groups: the Na/Ca exchangers (NCX; SLC8) and the Na/Ca+K exchangers (NCKX; SLC24). Two different NCX genes, NCX1 and NCX2, are highly expressed in brain. We recently described the widespread expression of 2 NCKX-type exchangers in brain, NCKX2 and NCKX3, and uncovered evidence for expression of another, NCKX4. The unique role that each different exchanger plays in neuronal calcium homeostasis, however, awaits further investigation. To begin exploring this central question, we examined both the expression pattern and the functional properties of the K-dependent Na/Ca exchanger isoforms expressed in brain and compared and contrasted these with NCX-type exchangers. Distinct patterns of transcript abundance, regional distribution, and developmental expression were noted for each isoform. Functional properties, including stoichiometry and the kinetic characteristics of ion binding, were determined for NCKX2 and are discussed in the context of cellular Ca2+ signaling.
Lytton
Jonathan
J
Cardiovascular Research Group, Department of Biochemistry & Molecular Biology, University of Calgary, Calgary, AB, Canada T2N 4N1. jlytton@ucalgary.ca
Li
Xaio-Fang
XF
Dong
Hui
H
Kraev
Alexander
A
D000595:Amino Acid Sequence; D000818:Animals; D017920:Antiporters / Q000235:genetics; D001921:Brain / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D019831:Sodium-Calcium Exchanger / Q000737:chemistry / Q000235:genetics / Q000502:physiology
D017920:Antiporters; C470570:SLC24A4 protein, human; C511589:Slc24a3 protein, mouse; D019831:Sodium-Calcium Exchanger; C110374:sodium-calcium exchanger 1; C074530:potassium-dependent sodium-calcium exchanger