title: 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.
abstract: The question of whether the activation of SOCs (store-operated Ca(2+) 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 Ca(2+) from different regions of the ER. TRPV1 was expressed in the ER and in the plasma membrane. The amount of Ca(2+) released from the ER by a TRPV1 agonist, measured using fura-2, was the same as that released by a SERCA (sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase) inhibitor, indicating that TRPV1 agonist-sensitive stores substantially overlap with SERCA inhibitor-sensitive stores. In contrast with SERCA inhibitors, TRPV1 agonists did not activate store-operated Ca(2+) entry. These findings were confirmed by patch-clamp recording. Using FFP-18, it was shown that SERCA inhibitors release Ca(2+) from the ER located closer to the plasma membrane than the region from which TRPV1 agonists release Ca(2+). In contrast with SERCA inhibitors, TRPV1 agonists did not induce a redistribution of STIM1 (stromal interaction molecule 1). TDCA caused the release of Ca(2+) 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, Ca(2+) release from a small component of the ER located near the plasma membrane is required to induce STIM1 redistribution and SOC activation.
authors.affiliation: Department of Medical Biochemistry, School of Medicine, Flinders University, Adelaide, South Australia 5001, Australia.
authors.forename: Joel
authors.initials: J
authors.lastname: Castro
authors.forename: Edoardo C
authors.initials: EC
authors.lastname: Aromataris
authors.forename: Grigori Y
authors.initials: GY
authors.lastname: Rychkov
authors.forename: Greg J
authors.initials: GJ
authors.lastname: Barritt
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology*; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006873:Hydroquinones / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D012430:Ruthenium Red / Q000494:pharmacology; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D050916:TRPV Cation Channels / Q000502:physiology*; D013657:Taurodeoxycholic Acid / Q000494:pharmacology; D014162:Transfection
chemical_list: D015220:Calcium Channels; D004224:Diterpenes; D006873:Hydroquinones; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D012430:Ruthenium Red; C019359:2,5-di-tert-butylhydroquinone; D013657:Taurodeoxycholic Acid; D015759:Ionomycin; C024353:resiniferatoxin; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium