GABA A Receptor Plasticity on Respiratory Neurons During Pregnancy Produces Barbiturate Insensitivity

Abstract

During pregnancy, rats experience extreme fluctuations in sex hormone levels. Neurosteroids fluctuate similarly and enhance the actions of GABA. Increased GABAA receptor function could cause excessive inhibition of respiration. It is unclear how respiratory neurons maintain homeostasis during pregnancy. We hypothesized that respiratory control is protected by an upregulation of GABAA receptor ε subunits during pregnancy in the ventral respiratory column (VRC). Insertion of ε subunits into GABAA receptors confers insensitivity to neurosteroids and barbiturates (GABAA receptor agonists). We used (1) in vivo phrenic nerve recording from male, virgin female, pregnant and postpartum rats to assess responses to increasing doses of pentobarbital, (2) in vitro recording from VRC neurons in slices to assess pentobarbital sensitivity, and (3) GABAA ε subunit immunoreactivity to show localization in the brainstem. In pregnant rats, phrenic activity was sustained in response to pentobarbital injection by comparison with all other groups. VRC neurons in vitro were insensitive to pentobarbital (300 μM), and GABAA receptor ε subunit immunoreactivity increased in the VRC in pregnant rats by comparison with other groups. These data suggest that insertion of the ε subunit into GABAA receptors in the VRC confers insensitivity to elevated neurosteroid levels during pregnancy. Supported by: AG18760 (MB), GM007507 (KH).