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CaT1 manifests the pore properties of the calcium-release-activated calcium channel

Nature volume 410, pages 705–709 (2001)Cite this article

Abstract

The calcium-release-activated Ca2+channel, ICRAC1,2,3, is a highly Ca2+-selective ion channel that is activated on depletion of either intracellular Ca2+ levels or intracellular Ca2+ stores. The unique gating of ICRAC has made it a favourite target of investigation for new signal transduction mechanisms; however, without molecular identification of the channel protein, such studies have been inconclusive. Here we show that the protein CaT1 (ref. 4), which has six membrane-spanning domains, exhibits the unique biophysical properties of ICRAC when expressed in mammalian cells. Like ICRAC, expressed CaT1 protein is Ca2+ selective, activated by a reduction in intracellular Ca2+ concentration, and inactivated by higher intracellular concentrations of Ca2+. The channel is indistinguishable from ICRAC in the following features: sequence of selectivity to divalent cations; an anomalous mole fraction effect; whole-cell current kinetics; block by lanthanum; loss of selectivity in the absence of divalent cations; and single-channel conductance to Na+ in divalent-ion-free conditions. CaT1 is activated by both passive and active depletion of calcium stores. We propose that CaT1 comprises all or part of the ICRAC pore.

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Figure 1: Currents in CaT1-expressing CHO-K1 cells.
Figure 2: CaT1 monovalent currents.
Figure 3: CaT1 single-channel properties (inside-out patch).
Figure 4: Activation of CaT1 currents.
Figure 5: Single-channel CaT1 currents.

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Acknowledgements

We thank M. D. Cahalan for discussion.

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Authors and Affiliations

  1. Howard Hughes Medical Institute,

    David E. Clapham

  2. Children's Hospital, Harvard Medical School, Enders 1309, 320 Longwood Avenue, Boston, 02115, Massachusetts, USA

    Lixia Yue & David E. Clapham

  3. Membrane Biology Program and Renal Division, Brigham and Women's Hospital and Harvard Medical School, Boston, 02115, Massachusetts, USA

    Ji-Bin Peng & Matthias A. Hediger

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  1. Lixia Yue
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  2. Ji-Bin Peng
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  3. Matthias A. Hediger
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  4. David E. Clapham
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Correspondence to David E. Clapham.

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Yue, L., Peng, JB., Hediger, M. et al. CaT1 manifests the pore properties of the calcium-release-activated calcium channel. Nature 410, 705–709 (2001). https://doi.org/10.1038/35070596

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