A small component of the endoplasmic reticulum is required for store-operated Ca2+ channel activation in liver cells: Evidence from studies using TRPV1 and taurodeoxycholic acid

Joel Castro, Edoardo C. Aromataris, Grigori Y. Rychkov, Greg J. Barritt

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23 Citations (Scopus)


The question of whether the activation of SOCs (store-operated Ca2+ channels) requires the whole or part of the ER (endoplasmic reticulum) has not been fully resolved. The role of a putative sub-compartment of the ER in SOC activation in liver cells was investigated using ectopically expressed TRPV1 (transient receptor potential vanilloid 1), a non-selective cation channel, and TDCA (taurodeoxycholic acid), an activator of SOCs, to release Ca2+ from different regions of the ER. TRPV1 was expressed in the ER and in the plasma membrane. The amount of Ca2+ released from the ER by a TRPV1 agonist, measured using fura-2, was the same as that released by a SERCA (sarcoplasmic/endoplasmic reticulum Ca2+-ATPase) inhibitor, indicating that TRPV1 agonistsensitive stores substantially overlap with SERCA inhibitor-sensitive stores. In contrast with SERCA inhibitors, TRPV1 agonists did not activate store-operated Ca2+ entry. These findings were confirmed by patch-clamp recording. Using FFP-18, it was shown that SERCA inhibitors release Ca2+ from the ER located closer to the plasma membrane than the region fromwhich TRPV1 agonists release Ca2+. In contrast with SERCA inhibitors, TRPV1 agonists did not induce a redistribution of STIM1 (stromal interaction molecule 1). TDCA caused the release of Ca2+ from the ER, which was detected by FFP-18 but not by fura-2, and a redistribution of STIM1 to puncta similar to that caused by SERCA inhibitors. It is concluded that in liver cells, Ca2+ release from a small component of the ER located near the plasma membrane is required to induce STIM1 redistribution and SOC activation.

Original languageEnglish
Pages (from-to)553-566
Number of pages14
JournalBiochemical Journal
Issue number3
Publication statusPublished or Issued - 15 Mar 2009


  • Bile acids
  • Calcium release
  • Endoplasmic reticulum
  • Store-operated calcium entry
  • Stromal interaction molecule 1 (STIM1)
  • Transient receptor potential vanilloid 1 (TRPV1)

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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