Activation-dependent properties of XXXX inhibition of GABAA receptor-mediated current.

@entity1246 @entity26003 @entity134 @entity230 @entity10768 @entity734
Sulfated @entity230 like @entity10768 (PS) are found endogenously in the central nervous system where they may modulate GABAA receptors. Understanding the mechanism of @entity134 inhibition is important for understanding the conditions under which endogenous @entity230 modulate GABAA receptor function, assessing their potential clinical utility, and for evaluating sulfated @entity230 as probes of receptor behaviour. Some previous studies suggest that sulfated @entity134 inhibition exhibits activation @entity734 , whilst other studies suggest only slow, time-dependent inhibition, perhaps reflecting slow PS association with receptors. We tested activation @entity734 in several ways. @entity134 potency increased 2- to 3-fold with approximately 10-fold change in @entity1246 concentration. PS inhibition of saturating partial agonist responses suggested that the level of channel activation, rather than receptor occupancy by agonist, is important for PS inhibition. Inhibition by sulfated @entity230 exhibited weak or no voltage @entity734 . Responses to rapid applications of exogenous @entity1246 differed little whether PS was pre-applied or simply co-applied with @entity1246 , consistent with the hypothesis that the actions of PS are facilitated by receptor activation. PS applied during steady-state @entity1246 responses exhibited slow onset and offset rate constants. The offset, rather than onset, was significantly slowed by elevated @entity1246 concentration. At hippocampal synapses, large, multiquantal IPSCs were inhibited more effectively by a fixed concentration of PS than small quantal content IPSCs, consistent with known 'pooling' of transmitter following multiquantal release. @entity26003 , although superficially similar to PS in its activation @entity734 , was dissimilar from PS in a number of details. In summary, PS inhibition exhibits activation @entity734 that may be explained by activation-dependent binding and altered desensitization.
