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OTRPC4, a nonselective cation channel that confers sensitivity to extracellular osmolarity

Abstract

Ca2+-permeable channels that are involved in the responses of mammalian cells to changes in extracellular osmolarity have not been characterized at the molecular level. Here we identify a new TRP (transient receptor potential)-like channel protein, OTRPC4, that is expressed at high levels in the kidney, liver and heart. OTRPC4 forms Ca2+-permeable, nonselective cation channels that exhibit spontaneous activity in isotonic media and are rapidly activated by decreases in, and are inhibited by increases in, extracellular osmolarity. Changes in osmolarity of as little as 10% result in significant changes in intracellular Ca2+ concentration. We propose that OTRPC4 is a candidate for a molecular sensor that confers osmosensitivity on mammalian cells.

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Figure 1: Close relatives of OTRPC4 and tissue distribution of the OTRPC4 transcript.
Figure 2: Localization of OTRPC4 in the kidney.
Figure 3: Ca2+ increase in OTRPC4-transfected HEK293 cells in response to a reduction in extracellular osmolarity.
Figure 4: Osmolarity-dependence of [Ca2+]i in fura-2-loaded HEK293 cells expressing OTRPC4.
Figure 5: Whole-cell currents in cells expressing OTRPC4.
Figure 6: Single-channel properties of OTRPC4 in cell-attached patches.

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Acknowledgements

We thank M. Schaefer for discussions and I. Reinsch for technical assistance. This work was supported by grants from the DFG and Fonds der Chemischen Industrie.

Correspondence and requests for materials should be addressed to T.D.P. The cDNA sequences encoding the mouse and the human OTRPC4 orthologues have been deposited at GenBank under accession numbers and AF208026, AF258465 respectively.

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Correspondence to Tim D. Plant.

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Correspondence and requests for materials should be addressed to T.D.P. The cDNA sequences encoding the mouse and the human OTRPC4 orthologues have been deposited at GenBank under accession numbers AF208026 and AF258465, respectively.

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Strotmann, R., Harteneck, C., Nunnenmacher, K. et al. OTRPC4, a nonselective cation channel that confers sensitivity to extracellular osmolarity. Nat Cell Biol 2, 695–702 (2000). https://doi.org/10.1038/35036318

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