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Membrane Transport Proteins and Receptors for Cadmium and Cadmium Complexes

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Cadmium Interaction with Animal Cells

Abstract

Cadmium (Cd2+) is a non-essential divalent metal ion without physiological function in animal cells. For toxicity to occur, Cd2+ must first enter cells by utilizing physiological transport pathways for essential divalent metal ions, such as Fe2+, Zn2+, Cu2+, Ca2+, or Mn2+. ‘Free’ Cd2+ ions and Cd2+ ions bound to small organic molecules are transported via ion channels, carrier proteins or ATP hydrolyzing pumps, whereas metalloproteins are internalized by receptor-mediated endocytosis (RME). This review describes Cd2+ transport (influx/efflux) pathways that were validated by electrophysiology (e.g. patch clamp), 109Cd2+ flux, inductively coupled plasma mass spectrometry, atomic absorption spectroscopy, Cd2+-sensitive fluorescent dyes, specific ligand binding, and ligand internalization assays that are ideally studied in heterologous expression systems. Convincing evidence has been obtained for Cd2+ permeation for Ca2+ channels at toxicologically relevant concentrations (CaV3.1, CatSper) TRP channels (TRPA1, TRPV5/6, TRPML1), solute carriers (DMT1, ZIP8, ZIP14, system (b0, + AT)) and RME of Cd2+-protein complexes (Lipocalin-2 receptor). The carrier OCT2 mediates Cd2+ influx and MATE1/2 and the ATPase ABCB1 Cd2+ efflux at high, toxicologically irrelevant Cd2+ concentrations. L- and N-type voltage-, ligand-gated, store-operated Ca2+ channels, CFTR, connexins and the transporter ferroportin-1 are not permeated by Cd2+. More experimental evidence is needed for the mitochondrial Ca2+ uniporter, the ATPase ABCC1 and the transferrin receptor 1. Although the receptor megalin: cubilin mediates RME of Cd2+-metallothionein complex at high, but toxicologically irrelevant concentrations, its in vivo Cd2+-protein–ligand complexes still need to be identified. A stringent methodology is mandatory to prove additional Cd2+ transport pathways instead of propagating unsubstantiated speculations.

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Acknowledgments

Research is supported by a grant from BMBF (01DN16039), the University of Witten/Herdecke and ZBAF. The author thanks Dr. Wing-Kee Lee (University of Witten/Herdecke) for valuable discussions.

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  1. Department of Physiology, Pathophysiology & Toxicology and Centre for Biomedical Education and Research (ZBAF), Faculty of Health, University of Witten/Herdecke, Stockumer Str. 12, 58453, Witten, Germany

    Frank Thévenod

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  1. Frank Thévenod
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Correspondence to Frank Thévenod .

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Editors and Affiliations

  1. Department of Physiology, Pathophysiology & Toxicology and ZBAF, Faculty of Health, School of Medicine, Witten/Herdecke University, Witten, Germany

    Frank Thévenod

  2. Department of Chemistry and Biochemistry, University of Wisconsin–Milwaukee, Milwaukee, WI, USA

    David Petering

  3. Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada

    Douglas M. Templeton

  4. Department of Physiology, Pathophysiology & Toxicology and ZBAF, Faculty of Health, School of Medicine, Witten/Herdecke University, Witten, Germany

    Wing-Kee Lee

  5. Department of Food Chemistry and Toxicology, Institute for Applied Biosciences, KIT, Karlsruhe, Baden-Württemberg, Germany

    Andrea Hartwig

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Thévenod, F. (2018). Membrane Transport Proteins and Receptors for Cadmium and Cadmium Complexes. In: Thévenod, F., Petering, D., M. Templeton, D., Lee, WK., Hartwig, A. (eds) Cadmium Interaction with Animal Cells. Springer, Cham. https://doi.org/10.1007/978-3-319-89623-6_1

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