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Allosteric activation of sodium–calcium exchange by picomolar concentrations of cadmium
Author(s) -
Dinh Le Hoa,
Omelchenko Alexander,
Hryshko Larry V.,
Uliyanova Alexandra,
Condrescu Madalina,
Reeves John P.
Publication year - 2005
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2004.077743
Subject(s) - allosteric regulation , cytosol , chemistry , chinese hamster ovary cell , biophysics , calcium , extracellular , microbiology and biotechnology , biochemistry , biology , enzyme , receptor , organic chemistry
Chinese hamster ovary cells expressing the bovine cardiac Na + –Ca 2+ exchanger (NCX1.1) accumulated Cd 2+ after a lag period of several tens of seconds. The lag period reflects the progressive allosteric activation of exchange activity by Cd 2+ as it accumulates within the cytosol. The lag period was greatly reduced in cells expressing a mutant exchanger, Δ(241‐680), that does not require allosteric activation by Ca 2+ for activity. Non‐transfected cells did not show Cd 2+ uptake under the same conditions. In cells expressing NCX1.1, the lag period was nearly abolished following an elevation of the cytosolic Ca 2+ concentration. Cytosolic Cd 2+ concentrations estimated at 0.5–2 p m markedly stimulated the subsequent uptake of Ca 2+ by Na + –Ca 2+ exchange. Outward exchange currents in membrane patches from Xenopus oocytes expressing the canine NCX1.1 were rapidly and reversibly stimulated by 3 p m Cd 2+ applied at the cytosolic membrane surface. Exchange currents activated by 3 p m Cd 2+ were 40% smaller than currents activated by 1 μ m cytosolic Ca 2+ . Current amplitudes declined by 30% and the rate of current development fell sharply upon repetitive applications of Na + in the presence of 3 p m Cd 2+ . Cd 2+ mimicked the anomalous inhibitory effects of Ca 2+ on outward exchange currents generated by the Drosophila exchanger CALX1.1. We conclude that the regulatory sites responsible for allosteric Ca 2+ activation bind Cd 2+ with high affinity and that Cd 2+ mimics the regulatory effects of Ca 2+ at concentrations 5 orders of magnitude lower than Ca 2+ .