title: Activation of endoplasmic reticulum calcium leak by 2-APB depends on the luminal calcium concentration.
abstract: It has been shown that 2-APB is a nonspecific modulator of ion channel activity, while most of the channels are inhibited by this compound, there are few examples of channels that are activated by 2-APB. Additionally, it has been shown that, 2-APB leads to a reduction in the luminal endoplasmic reticulum Ca2+level ([Ca2+]ER) and we have carried out simultaneous recordings of both [Ca2+]iand the [Ca2+]ERin HeLa cell suspensions to assess the mechanism involved in this effect. This approach allowed us to determine that 2-APB induces a reduction in the [Ca2+]ERby activating an ER-resident Ca2+permeable channel more than by inhibiting the activity of SERCA pumps. Interestingly, this effect of 2-APB of reducing the [Ca2+]ERis auto-limited because depends on a replete ER Ca2+store; a condition that thapsigargin does not require to decrease the [Ca2+]ER. Additionally, our data indicate that the ER Ca2+permeable channel activated by 2-APB does not seem to participate in the ER Ca2+leak revealed by inhibiting SERCA pump with thapsigargin. This work suggests that, prolonged incubations with even low concentrations of 2-APB (5μM) would lead to the reduction in the [Ca2+]ERthat might explain the inhibitory effect of this compound on those signals that require Ca2+release from the ER store.
authors.affiliation: Departamento de Bioquímica, Cinvestav, 07000 Mexico City, Mexico.
authors.forename: Daniel
authors.initials: D
authors.lastname: Leon-Aparicio
authors.affiliation: Departamento de Bioquímica, Cinvestav, 07000 Mexico City, Mexico.
authors.forename: Jesus
authors.initials: J
authors.lastname: Chavez-Reyes
authors.affiliation: Departamento de Bioquímica, Cinvestav, 07000 Mexico City, Mexico. Electronic address: aguerrero@cinvestav.mx.
authors.forename: Agustin
authors.initials: A
authors.lastname: Guerrero-Hernandez
mesh_terms: D001896:Boron Compounds / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D001896:Boron Compounds; D019284:Thapsigargin; C109986:2-aminoethoxydiphenyl borate; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium
keywords: 2-APB; Calcium leak; Luminal endoplasmic reticulum calcium concentration; SERCA pump; Thapsigargin