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J Physiol
2005 Feb 15;563Pt 1:105-17. doi: 10.1113/jphysiol.2004.077743.
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Allosteric activation of sodium-calcium exchange by picomolar concentrations of cadmium.
Le HD
,
Omelchenko A
,
Hryshko LV
,
Uliyanova A
,
Condrescu M
,
Reeves JP
.
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Chinese hamster ovary cells expressing the bovine cardiac Na+-Ca2+ exchanger (NCX1.1) accumulated Cd2+ after a lag period of several tens of seconds. The lag period reflects the progressive allosteric activation of exchange activity by Cd2+ as it accumulates within the cytosol. The lag period was greatly reduced in cells expressing a mutant exchanger, Delta(241-680), that does not require allosteric activation by Ca2+ for activity. Non-transfected cells did not show Cd2+ uptake under the same conditions. In cells expressing NCX1.1, the lag period was nearly abolished following an elevation of the cytosolic Ca2+ concentration. Cytosolic Cd2+ concentrations estimated at 0.5-2 pm markedly stimulated the subsequent uptake of Ca2+ by Na+-Ca2+ exchange. Outward exchange currents in membrane patches from Xenopus oocytes expressing the canine NCX1.1 were rapidly and reversibly stimulated by 3 pm Cd2+ applied at the cytosolic membrane surface. Exchange currents activated by 3 pm Cd2+ were 40% smaller than currents activated by 1 mum cytosolic Ca2+. Current amplitudes declined by 30% and the rate of current development fell sharply upon repetitive applications of Na+ in the presence of 3 pm Cd2+. Cd2+ mimicked the anomalous inhibitory effects of Ca2+ on outward exchange currents generated by the Drosophila exchanger CALX1.1. We conclude that the regulatory sites responsible for allosteric Ca2+ activation bind Cd2+ with high affinity and that Cd2+ mimics the regulatory effects of Ca2+ at concentrations 5 orders of magnitude lower than Ca2+.
Aceto,
Cloning and expression of the bovine cardiac sodium-calcium exchanger.
1992, Pubmed,
Xenbase
Aceto,
Cloning and expression of the bovine cardiac sodium-calcium exchanger.
1992,
Pubmed
,
Xenbase
Bers,
A practical guide to the preparation of Ca2+ buffers.
1994,
Pubmed
Blaustein,
Sodium/calcium exchange: its physiological implications.
1999,
Pubmed
Bressler,
Divalent metal transporter 1 in lead and cadmium transport.
2004,
Pubmed
Chernysh,
Calcium-dependent regulation of calcium efflux by the cardiac sodium/calcium exchanger.
2004,
Pubmed
Condrescu,
Barium influx mediated by the cardiac sodium-calcium exchanger in transfected Chinese hamster ovary cells.
1997,
Pubmed
DiPolo,
Calcium influx in internally dialyzed squid giant axons.
1979,
Pubmed
Egger,
Functional expression of the human cardiac Na+/Ca2+ exchanger in Sf9 cells: rapid and specific Ni2+ transport.
1999,
Pubmed
Egger,
Ni2+ transport by the human Na+/Ca2+ exchanger expressed in Sf9 cells.
1999,
Pubmed
Frame,
Mn and Cd transport by the Na-Ca exchanger of ferret red blood cells.
1991,
Pubmed
Grynkiewicz,
A new generation of Ca2+ indicators with greatly improved fluorescence properties.
1985,
Pubmed
Hilgemann,
Regulation and deregulation of cardiac Na(+)-Ca2+ exchange in giant excised sarcolemmal membrane patches.
1990,
Pubmed
Hilgemann,
The cardiac Na-Ca exchanger in giant membrane patches.
1996,
Pubmed
Hryshko,
Anomalous regulation of the Drosophila Na(+)-Ca2+ exchanger by Ca2+.
1996,
Pubmed
,
Xenbase
Iwamoto,
A novel isothiourea derivative selectively inhibits the reverse mode of Na+/Ca2+ exchange in cells expressing NCX1.
1996,
Pubmed
Iwamoto,
Na+/Ca2+ exchanger overexpression impairs calcium signaling in fibroblasts: inhibition of the [Ca2+] increase at the cell periphery and retardation of cell adhesion.
1998,
Pubmed
Järup,
Hazards of heavy metal contamination.
2003,
Pubmed
KAGI,
Metallothionein: a cadmium and zinc-containign protein from equine renal cortex. II. Physico-chemical properties.
1961,
Pubmed
Klaassen,
Metallothionein transgenic and knock-out mouse models in the study of cadmium toxicity.
1998,
Pubmed
Klaassen,
Metallothionein: an intracellular protein to protect against cadmium toxicity.
1999,
Pubmed
Langille,
ADP-ribosylation factor 6 as a target of guanine nucleotide exchange factor GRP1.
1999,
Pubmed
Levitsky,
Identification of the high affinity Ca(2+)-binding domain of the cardiac Na(+)-Ca2+ exchanger.
1994,
Pubmed
Limaye,
Cytotoxicity of cadmium and characteristics of its transport in cardiomyocytes.
1999,
Pubmed
Lytton,
Thapsigargin inhibits the sarcoplasmic or endoplasmic reticulum Ca-ATPase family of calcium pumps.
1991,
Pubmed
Matsuoka,
Initial localization of regulatory regions of the cardiac sarcolemmal Na(+)-Ca2+ exchanger.
1993,
Pubmed
,
Xenbase
Nath,
Metallothioneins, oxidative stress and the cardiovascular system.
2000,
Pubmed
Navas-Acien,
Lead, cadmium, smoking, and increased risk of peripheral arterial disease.
2004,
Pubmed
Omelchenko,
Functional differences in ionic regulation between alternatively spliced isoforms of the Na+-Ca2+ exchanger from Drosophila melanogaster.
1998,
Pubmed
,
Xenbase
Philipson,
The Na+/Ca2+ exchange molecule: an overview.
2002,
Pubmed
Pourahmad,
Carcinogenic metal induced sites of reactive oxygen species formation in hepatocytes.
2003,
Pubmed
Reeves,
Lanthanum is transported by the sodium/calcium exchanger and regulates its activity.
2003,
Pubmed
Reeves,
Allosteric activation of sodium-calcium exchange activity by calcium: persistence at low calcium concentrations.
2003,
Pubmed
Shigekawa,
Cardiac Na(+)-Ca(2+) exchange: molecular and pharmacological aspects.
2001,
Pubmed
Thévenod,
Nephrotoxicity and the proximal tubule. Insights from cadmium.
2003,
Pubmed
Trac,
Transport and regulation of the cardiac Na(+)-Ca2+ exchanger, NCX1. Comparison between Ca2+ and Ba2+.
1997,
Pubmed
,
Xenbase
Trosper,
Effects of divalent and trivalent cations on Na+-Ca2+ exchange in cardiac sarcolemmal vesicles.
1983,
Pubmed
Waalkes,
Cadmium carcinogenesis.
2003,
Pubmed
Waisberg,
Molecular and cellular mechanisms of cadmium carcinogenesis.
2003,
Pubmed
Wang,
Cadmium inhibits the electron transfer chain and induces reactive oxygen species.
2004,
Pubmed