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

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.