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Issue 976 coverCELLULAR AND MOLECULAR PHYSIOLOGY OF SODIUM-CALCIUM EXCHANGE: PROCEEDINGS OF THE FOURTH INTERNATIONAL CONFERENCE Copyright © 2002 by the New York Academy of Sciences
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Annals of the New York Academy of Sciences 976:382-393 (2002)
© 2002 New York Academy of Sciences

K+-Dependent Na+/Ca2+ Exchangers in the Brain

JONATHAN LYTTONa, XIAO-FANG LIa, HUI DONGa AND ALEXANDER KRAEVb

aCardiovascular Research Group, Departments of Biochemistry & Molecular Biology and Physiology & Biophysics, University of Calgary, Calgary, AB, Canada T2N 4N1
bSamuel Lunenfeld Research Institute, Mt. Sinai Hospital, Toronto, ON, Canada M5G 1X5

Address for correspondence: Jonathan Lytton, Ph.D., Department of Biochemistry & Molecular Biology, University of Calgary Health Sciences Centre, Room 2518, 3330 Hospital Drive NW, Calgary, AB, Canada T2N 4N1. Voice: 403-220-2893; fax: 403-283-4841.
jlytton{at}ucalgary.ca
Ann. N.Y. Acad. Sci. 976: 382-393 (2002).

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.

Key Words: Northern blotting • in situ hybridization • recombinant expression • stoichiometry




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