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This Article Full Text Full Text (PDF) All Versions of this Article: 563/1/105    most recent jphysiol.2004.077743v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Le, H. D. Articles by Reeves, J. P Search for Related Content PubMed PubMed Citation Articles by Le, H. D. Articles by Reeves, J. P

¹ Institute of Cardiovascular Sciences, University of Manitoba, St Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada, R2H 2A6
² Department of Pharmacology & Physiology, University of Medicine and Dentistry of New Jersey, 185 South Orange Avenue, Newark, NJ 07103, USA

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, (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 µM 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⁺.

(Received 19 October 2004; accepted after revision 16 December 2004; first published online 20 December 2004)
Corresponding author J. P. Reeves: Department of Pharmacology & Physiology, University of Medicine and Dentistry of New Jersey, 185 South Orange Avenue, Newark, NJ 07103, USA. Email: reeves{at}umdnj.edu

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