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TRPM3 channels provide a regulated influx pathway for zinc in pancreatic beta cells

  • Ion Channels, Receptors and Transporters
  • Published:
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Abstract

Zinc is stored in insulin-containing dense core vesicles of pancreatic β-cells where it forms crystals together with insulin and calcium ions. Zinc ions are therefore released together with insulin upon exocytosis of these vesicles. Consequently, pancreatic β-cells need to take up large amounts of zinc from the extracellular space across their plasma membrane. The pathways for zinc uptake are only partially understood. TRPM3 channels are present in pancreatic β-cells and can be activated by the endogenous steroid pregnenolone sulfate. We demonstrate here that recombinant TRPM3 channels are highly permeable for many divalent cations, in particular also for zinc ions. Importantly, TRPM3 channels endogenously expressed in pancreatic β-cells are also highly permeable for zinc ions. Using FluoZin3 to image changes of the intracellular zinc concentration, we show that pancreatic β-cells take up zinc through TRPM3 channels even when extracellular zinc concentrations are low and physiological levels of calcium and magnesium are present. Activation of TRPM3 channels also leads to depolarization of β-cells and to additional zinc influx through voltage-gated calcium channels. Our data establish that TRPM3 channels constitute a regulated entry pathway for zinc ions in pancreatic β-cells.

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Acknowledgments

We thank Sandra Plant, Melanie Portz, Heidi Löhr, and Martin Simon-Thomas for excellent technical support. We also thank Oleksandr Rizun for critically reading the manuscript and Dr. Veit Flockerzi for his support during this study. This work was financially supported by the DFG (Emmy Noether Program and GK 1326), HOMFOR, and Forschungskommission der Universität des Saarlandes.

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  1. Thomas F. J. Wagner

    Present address: Department of Cell Biology, Institute for Childhood and Neglected Disease, The Scripps Research Institute, La Jolla, CA, 92037, USA

Authors and Affiliations

  1. Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universitätsklinikum des Saarlandes, Gebäude 46, 66421, Homburg, Germany

    Thomas F. J. Wagner, Anna Drews, Sabine Loch, Florian Mohr, Stephan E. Philipp, Sachar Lambert & Johannes Oberwinkler

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  1. Thomas F. J. Wagner
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Correspondence to Johannes Oberwinkler.

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Thomas F.J. Wagner, Anna Drews, Sabine Loch, Florian Mohr, Sachar Lambert, and Johannes Oberwinkler are members of the Emmy Noether Research Group in the Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universitätsklinikum des Saarlandes.

Anna Drews and Sabine Loch contributed equally to this work.

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Wagner, T.F.J., Drews, A., Loch, S. et al. TRPM3 channels provide a regulated influx pathway for zinc in pancreatic beta cells. Pflugers Arch - Eur J Physiol 460, 755–765 (2010). https://doi.org/10.1007/s00424-010-0838-9

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  • DOI: https://doi.org/10.1007/s00424-010-0838-9

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