Effects of Adenophostin-A and Inositol-1,4,5-trisphosphate on Cl− Currents in Xenopus laevis Oocytes

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Abstract
Adenophostin-A, a novel compound isolated from cultures ofPenicillium brevicompactum, has been shown to stimulate Ca2+ release from inositol-1,4,5-trisphosphate (IP3)-sensitive Ca2+ stores in microsomal preparations, permeabilized cells, and lipid vesicles containing purified IP3 receptor. The purpose of the current study was to compare the effects of adenophostin-A and IP3 on Ca2+ release from stores and Ca2+ influx in intact Xenopus laevis oocytes. Ca2+ influx though store-operated Ca2+ channels and Ca2+release from stores were monitored by measuring two Ca2+-activated Cl− currents that can be used as real-time indicators of Ca2+ release and Ca2+ influx (ICl-1 and ICl-2, respectively). We find that high concentrations (final intraoocyte concentrations of 5–10 μm) of adenophostin-A and IP3 stimulate a large Ca2+ release from stores (as measured by ICl-1) followed by Ca2+ influx (as measured by ICl-2). Low concentrations (∼50 nm) of IP3 stimulate oscillations in Ca2+ release without stimulating Ca2+ influx. In contrast, low concentrations of adenophostin-A can stimulate Ca2+ influx without stimulating a large Ca2+ release. However, Ca2+ influx did not occur in the complete absence of Ca2+ release. Therefore, it is unlikely that adenophostin-A directly stimulates store-operated Ca2+ channels. We hypothesize that adenophostin-A releases Ca2+ from a subpopulation of stores that is tightly coupled to store-operated Ca2+ channels.