FIGURE 7.

The highly selective inhibitor of PP2A fostriecin has no effect on I_Cl(Ca) recorded in the absence of internal ATP. A (a), plot showing the time course of changes of mean normalized late I_Cl(Ca) recorded at +90 mV (1-s steps at 10-s intervals) in cells dialyzed with no ATP, in the presence (empty squares; n = 10) or absence (filled squares; n = 7) of 30 nm fostriecin, a concentration ∼10-fold higher than the IC₅₀ for PP2A (3.2 nm). At this concentration, the compound failed to alter I_Cl(Ca) amplitude at +90 mV during the initial rundown and late recovery over the course of 20 min. A (b), similar graph to that shown in A (a) except that for these experiments, fostriecin concentration was raised to 150 nm (47-fold higher than the IC₅₀ for PP2A). Data obtained with (empty squares) or without (filled squares) fostriecin were obtained from 7 and 10 cells, respectively. Similar to the results illustrated previously, this concentration of fostriecin was unsuccessful in attenuating the recovery of late I_Cl(Ca). B, current-voltage relationships for late I_Cl(Ca) in cells dialyzed with 0 ATP, in the absence (filled squares; n = 3) or presence of 30 (empty squares; n = 3) or 150 nm (empty circles; n = 2) fostriecin. All I-V values were obtained immediately following the conclusion of the 20-min test protocol. Consistent with the data presented in A, this graph illustrates the lack of effect of fostriecin on I_Cl(Ca) at voltages ranging from −100 to +130 mV. n.s., not significant (all panels).