Modulation of the human ρ1 GABAA receptor by inhibitory steroids.

ABSTRACT:

Rationale

Modulators of the ρ1 GABAA receptor may be useful in the treatment of visual, sleep, and cognitive disorders. Neuroactive steroids and analogues have been shown to modulate ρ1 receptor function, but the molecular mechanisms are poorly understood.

Objectives

We employed electrophysiology and voltage-clamp fluorometry to compare the actions of several neuroactive steroids and analogues on the human ρ1 GABAA receptor.

Results

Results confirmed that P294S and T298F mutations affect modulation by steroids. The P294S mutation abolished inhibition by (3α,5β)-3-hydroxypregnan-20-one (3α5βP) while the T298F mutation eliminated inhibition by 17β-estradiol. Voltage-clamp fluorometry demonstrated that steroids differing in the presence of a charged group on C3 or nature

SUBMITTER: Eaton MM 

PROVIDER: S-EPMC4048647 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature