β2-nicotinic acetylcholine receptor promotes development of GABAA receptors in mouse hippocampal CA1 and CA3 pyramidal neurons

Abstract

To explore the role of β2-nicotinic acetylcholine receptor (β2-nAChR) in the development of γ- aminobutyric acid A type receptors (GABAA-Rs) in hippocampal CA1 and CA3 pyramidal neurons of mice. The hippocampal CA1 and CA3 pyramidal neurons were acutely isolated from β2-nAChR gene knockout (β2-KO group) mice. GABA currents in CA1 and CA3 pyramidal neurons were induced with the selective GABAA-R agonist muscimol and recorded using perforated patch-clamp recording technique. The GABA currents of CA1 and CA3 pyramidal neurons were tested for their equilibrium potentials (EMuss) and kinetic parameters and were compared with the measurements in wild-type mice (WT group). The mean EMus of CA1 neurons (n=7) of β2-KO mice (n=4) was -31.7±3.5 mV, showing an obvious depolarizing shift compared with the WT mice (P < 0.05); the mean EMus of CA3 neurons (n=4) was -16.1±4.6 mV, also showing a depolarizing shift (P < 0.01). The difference in the EMuss between CA3 and CA1 neurons in β2-KO mice, but not in WT mice, was significant (P < 0.05). The GABAA-R desensitization was significantly slowed down in both CA1 and CA3 neurons of β2-KO mice, with decay time of 2.2±0.2 s and 3.2±0.1 s, respectively, significantly longer than those in WT mice (1.6±0.1 s and 2.3±0.1 s, respectively; P < 0.05). β2-containing nAChRs may promote the functional maturation of GABAA-R in CA1 and CA3 pyramidal cells in mouse hippocampus.