SERCA2b and 3 play a regulatory role in store-operated calcium entry in human platelets

Cell Signal. 2008 Feb;20(2):337-46. doi: 10.1016/j.cellsig.2007.10.019. Epub 2007 Oct 26.


Two agonist-releasable Ca(2+)stores have been identified in human platelets differentiated by the distinct sensitivity of their SERCA isoforms to thapsigargin (TG) and 2,5-di-(tert-butyl)-1,4-hydroquinone (TBHQ). Here we have examined whether the SERCA isotypes might be involved in store-operated Ca(2+)entry (SOCE) activated by the physiological agonist thrombin in human platelets. Ca(2+)-influx evoked by thrombin (0.01 U/mL) reached a maximum after 3 min, which was consistent with the decrease in the Ca(2+)content in the stores; afterwards, the extent of SOCE decreased with no correlation with the accumulation of Ca(2+)in the stores. Inhibition of SERCA2b, by 10 nM TG, and SERCA3, with 20 microM TBHQ, individually or simultaneously, accelerated Ca(2+) store discharge and subsequently enhanced the extent of SOCE stimulated by thrombin. In addition, TG and TBHQ modified the time course of thrombin-evoked SOCE from a transient to a sustained increase in Ca(2+) influx, which reveals a negative role for SERCAs in the regulation of SOCE. This effect was consistent under conditions that inhibit Ca(2+) extrusion by PMCA or the Na(+)/Ca(2+) exchanger. Coimmunoprecipitation experiments revealed that thrombin stimulates direct interaction between SERCA2b and 3 with the hTRPC1 channel, an effect that was found to be independent of SERCA activity. In summary, our results suggest that SERCA2b and 3 modulate thrombin-stimulated SOCE probably by direct interaction with the hTRPC1 channel in human platelets.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Platelets / drug effects
  • Blood Platelets / enzymology*
  • Calcium / metabolism
  • Calcium Signaling* / drug effects
  • Humans
  • Immunoprecipitation
  • Inositol 1,4,5-Trisphosphate Receptors / metabolism
  • Isoenzymes / metabolism
  • Protein Binding / drug effects
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / antagonists & inhibitors
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / metabolism*
  • TRPC Cation Channels / metabolism
  • Thrombin / pharmacology
  • Time Factors


  • Inositol 1,4,5-Trisphosphate Receptors
  • Isoenzymes
  • TRPC Cation Channels
  • transient receptor potential cation channel, subfamily C, member 1
  • Thrombin
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • ATP2A2 protein, human
  • ATP2A3 protein, human
  • Calcium