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

Abstract

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 (0.3–1000 μM)- and muscimol (100–1000 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.