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Anomalous regulation of the Drosophila Na^+-Ca^(2+) exchanger by Ca^(2+)

Hryshko, Larry V. and Matsuoka, Satoshi and Nicoll, Debora A. and Weiss, James N. and Schwarz, Erich M. and Benzer, Seymour and Philipson, Kenneth D. (1996) Anomalous regulation of the Drosophila Na^+-Ca^(2+) exchanger by Ca^(2+). Journal of General Physiology, 108 (1). pp. 67-74. ISSN 0022-1295. PMCID PMC2229296. doi:10.1085/jgp.108.1.67.

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The Na^+-Ca^(2+) exchanger from Drosophila was expressed in Xenopus and characterized electrophysiologically using the giant excised patch technique. This protein, termed Calx, shares 49% amino acid identity to the canine cardiac Na^+-Ca^(2+) exchanger, NCX1. Calx exhibits properties similar to previously characterized Na^+-Ca^(2+) exchangers including intracellular Na^+ affinities, current-voltage relationships, and sensitivity to the peptide inhibitor, XIP. However, the Drosophila Na^+-Ca^(2+) exchanger shows a completely opposite response to cytoplasmic Ca^(2+). Previously cloned Na^+-Ca^(2+) exchangers (NCX1 and NCX2) are stimulated by cytoplasmic Ca^(2+) in the micromolar range (0.1-10 microM). This stimulation of exchange current is mediated by occupancy of a regulatory Ca^(2+) binding site separate from the Ca^(2+) transport site. In contrast, Calx is inhibited by cytoplasmic Ca^(2+) over this same concentration range. The inhibition of exchange current is evident for both forward and reverse modes of transport. The characteristics of the inhibition are consistent with the binding of Ca^(2+) at a regulatory site distinct from the transport site. These data provide a rational basis for subsequent structure-function studies targeting the intracellular Ca^(2+) regulatory mechanism.

Item Type:Article
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Schwarz, Erich M.0000-0003-3151-4381
Alternate Title:Anomalous regulation of the Drosophila Na+-Ca2+ exchanger by Ca2+
Additional Information:© 1996 Rockefeller University Press. After the Initial Publication Period, RUP will grant to the public the non-exclusive right to copy, distribute, or display the Article under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 International license, as described at, or updates thereof. Original version received 3 January 1996 and accepted version received 2 April 1996. This work was supported by National Institutes of Health (NIH) grants HL48509 and HL49101 to K.D. Philipson, NIH grants EY09278 and AG12289, National Science Foundation grant MCB9408718, grants from the James G. Boswell Foundation to S. Benzer, grants from the Beckman Institute at Caltech to E. Schwarz, Medical Research Council and Heart and Stroke Foundation grants to L.V. Hryshko, and by American Heart Association grants, Greater Los Angeles Affiliate to D.A. Nicoll and L.V. Hryshko. A preliminary report of this work has appeared in abstract form (Hryshko, L.V., D.A. Nicoll, S. Matsuoka, J.N. Weiss, E. Schwarz, S. Benzer, and K.D. Philipson. 1995. Biophys.J. 68:410a).
Funding AgencyGrant Number
James G. Boswell FoundationUNSPECIFIED
Caltech Beckman InstituteUNSPECIFIED
Medical Research Council (Canada)UNSPECIFIED
Heart and Stroke Foundation of CanadaUNSPECIFIED
American Heart Association, Greater Los Angeles AffiliateUNSPECIFIED
Subject Keywords:sodium-calcium exchange; calcium regulation; Drosophila melanogaster
Issue or Number:1
PubMed Central ID:PMC2229296
Record Number:CaltechAUTHORS:20190228-115828088
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Official Citation:Anomalous regulation of the Drosophila Na(+)-Ca2+ exchanger by Ca2+. L V Hryshko, S Matsuoka, D A Nicoll, J N Weiss, E M Schwarz, S Benzer, K D Philipson The Journal of General Physiology Jul 1996, 108 (1) 67-74; DOI: 10.1085/jgp.108.1.67
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:93351
Deposited By: George Porter
Deposited On:28 Feb 2019 20:57
Last Modified:16 Nov 2021 16:57

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