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Store-operated Ca2+ entry in platelets occurs independently of transient receptor potential (TRP) C1

  • Ion Channels, Receptors and Transporters
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Abstract

Changes in [Ca2+]i are a central step in platelet activation. In nonexcitable cells, receptor-mediated depletion of intracellular Ca2+ stores triggers Ca2+ entry through store-operated calcium (SOC) channels. Stromal interaction molecule 1 (STIM1) has been identified as an endoplasmic reticulum (ER)-resident Ca2+ sensor that regulates store-operated calcium entry (SOCE), but the identity of the SOC channel in platelets has been controversially debated. Some investigators proposed transient receptor potential (TRP) C1 to fulfil this function based on the observation that antibodies against the channel impaired SOCE in platelets. However, others could not detect TRPC1 in the plasma membrane of platelets and raised doubts about the specificity of the inhibiting anti-TRPC1 antibodies. To address the role of TRPC1 in SOCE in platelets, we analyzed mice lacking TRPC1. Platelets from these mice display fully intact SOCE and also otherwise unaltered calcium homeostasis compared to wild-type. Furthermore, platelet function in vitro and in vivo is not altered in the absence of TRPC1. Finally, studies on human platelets revealed that the presumably inhibitory anti-TRPC1 antibodies have no specific effect on SOCE and fail to bind to the protein. Together, these results provide evidence that SOCE in platelets is mediated by channels other than TRPC1.

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Acknowledgement

We would like to thank Sylvia Hengst for the excellent technical support. This work was supported by grant Ni556/7-1 and the SFB 688 from the Deutsche Forschungsgemeinschaft (DFG) (to B.N.). AA is supported by the Medical Research Council (UK), and KSA is supported by the British Heart Foundation.

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Authors and Affiliations

  1. Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine, University of Würzburg, Zinklesweg 10, 97078, Würzburg, Germany

    David Varga-Szabo, Attila Braun, Markus Bender & Bernhard Nieswandt

  2. Cardiovascular Division, King’s College London, Franklin Wilkins Building, Stamford Street, London, SE1 9NH, UK

    Kalwant S. Authi, Archana Ambily & Sheila R. Hassock

  3. Department of Pharmacology and Toxicology, Philipps-Universität Marburg, Marburg, Germany

    Thomas Gudermann & Alexander Dietrich

  4. Institute of Clinical Biochemistry and Pathobiochemistry, University of Würzburg, Würzburg, Germany

    Bernhard Nieswandt

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  1. David Varga-Szabo
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  2. Kalwant S. Authi
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Correspondence to Bernhard Nieswandt.

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David Varga-Szabo and Kalwant S. Authi contributed equally to this article.

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Varga-Szabo, D., Authi, K.S., Braun, A. et al. Store-operated Ca2+ entry in platelets occurs independently of transient receptor potential (TRP) C1. Pflugers Arch - Eur J Physiol 457, 377–387 (2008). https://doi.org/10.1007/s00424-008-0531-4

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  • DOI: https://doi.org/10.1007/s00424-008-0531-4

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