Inhibitory effect of baclofen on GABA-induced depolarization and GABA- activated current in primary sensory neurons

It has been established that GABA(A) and GABA(B) receptors can exist separately and/or co-exist in the membrane of dorsal root ganglion neurons. In our previous investigation it has been shown that co-existence of these two kinds of receptors is about 80% of the neurons examined (20/25). The present study was aimed to explore whether the activation of these two kinds of receptors could interact with each other using intracellular and whole- cell patch-clamp recordings. Baclofen, a specific GABA(B) receptor agonist, was found to exert negative modulatory effects on the responses mediated by GABA(A) receptor. In experiments with intracellular recording, GABA (03-1000 μM)- and muscimol (00-1000 μM)-induced depolarization was attenuated markedly and reversibly by preapplication of baclofen (100 μM) (15/21 and 17/21, respectively). In whole-cell patch-clamp recordings GABA (100 μM) and two specific GABA(A) receptor agonists, muscimol (10 μM) and isoguvacine (50 μM), activated currents were inhibited markedly by preapplication of baclofen 30 s or more and the inhibition was concentration dependent (1-100 μM baclofen) and reversible. The possible mechanisms underlying the inhibition by baclofen of the responses mediated by GABA(A) receptor and the physiological significance implicated are discussed.