Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5530483 | Cell Calcium | 2017 | 11 Pages |
â¢2-APB reduces the endoplasmic reticulum [Ca2+] by activating a leak channel.â¢2-APB needs a store replete with Ca2+ for inducing a Ca2+ leak.â¢The channel activated by 2-APB is not permanently open.â¢This channel does not participate in the ER Ca2+ leak revealed by thapsigargin.â¢2-APB partially inhibits the ER Ca2+ leak after thapsigargin.
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+]i and the [Ca2+]ER in 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+]ER by 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+]ER is 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 (5 μM) would lead to the reduction in the [Ca2+]ER that might explain the inhibitory effect of this compound on those signals that require Ca2+ release from the ER store.
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