The actions of 3-aminopropanephosphinic acid at GABA_B receptors in rat hippocampus

The actions of 3-aminopropanephosphinic acid (APPA) were examined using whole-cell patch-clamp recording in rat hippocampal slice. In recordings from neurons in subfield CA1 of slices from young (2-4 weeks) and adult (> 2 month) rats, APPA (0.5-50 μM) produced membrane hyperpolarization and outward current under voltage-clamp. APPA also inhibited excitatory postsynaptic potentials with an IC₅₀ of 2.3 μM, and reduced inhibitory postsynaptic potentials at concentrations from 0.1 to 1 μM. The hyperpolarizing and synaptic depressant effects of APPA were reduced by 2-OH-saclofen an antagonist at the B-type receptor for the neurotransmitter γ-aminobutyric acid (GABA). In this preparation APPA exhibited potencies similar to those previously reported for the GABA_B receptor agonist baclofen. APPA was much less effective in inhibiting synaptic transmission measured using field potential recordings. The observations made with whole-cell patch-clamp recording indicate that in hippocampus APPA acts as a potent agonist at presynaptic GABA_B receptors associated with both excitatory and inhibitory synapses, and also activates postsynaptic GABA_B receptors.