Neuroactive steroids have multiple actions to potentiate GABAA receptors

摘要: The effects of neuroactive steroids on the function GABAA receptors were studied using cell-attached records single channel activity recorded from HEK293 cells transfected with α1 β2 γ2L subunits. Activity was elicited a half-maximal (50 μm) concentration GABA. Two in detail: ACN ((3α,5α,17β)-3-hydroxyandrostane-17-carbonitrile) and B285 ((3α,5β,17β)-3-hydroxy-18-norandrostane-17-carbonitrile). Four seen, two open time distributions closed times. When clusters openings absence steroid, distribution contained three components. produced concentration-dependent alterations distribution. prevalence longest duration class times increased about 15% to 40% (EC50 180 nm ACN), while 7.4 ms 27 35 ACN). also 18 B285) but only at concentrations close 10 μm. differences actions these suggest that proportion long component are by independent mechanisms there separate recognition sites for which associated functional actions. showed components steroid. rate occurrence brief decreased increasing ACN, an EC50 50 ACN. In contrast, did not reduce closings until high applied. However, both reduced activation-related state selectively, comparable IC50 (about 40 20 B285). As case action data mechanisms, perhaps presence of  1 μm had no effect estimated opening or apparent affinity receptor Mutation carboxy terminus γ2 subunit, subunits, abolished ability increase OT3 reduction state. These observations consistent idea is more than one distinguishable steroid site receptor.