GABA(A) receptor modulates the activity of inner hair cell afferents in guinea pig cochlea

Abstract

The inhibitory neurotransmitter gamma-aminobutyric acid (GABA) is mediated by two main categories of receptors: the GABA(A) and GABA(B) receptor. Recent immunocytochemical and electron microscopical studies revealed the existence of GABA at the efferent olivocochlear innervation of the guinea pig cochlea. In this microiontophoretic study we examined the effect of GABA on spontaneous and glutamate or acetylcholine induced activity of afferent fibres in the dendritic region of inner hair cells. Furthermore, the receptor subtypes being responsible for this GABA action were analysed using specific agonists and antagonists on alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and N-methyl-D-aspartic acid (NMDA) induced activity. The spike activities of the subsynaptic area were recorded in the third or fourth turn of the cochlea of anaesthetised guinea pigs. Application of GABA had little effect on spontaneous activity whereas the glutamate or acetylcholine induced firing rate could be depressed by GABA. AMPA and NMDA induced activity was reduced by the GABA(A) agonist muscimol but not by the GABA(B) agonist baclofen. The GABA(A) antagonist blocked the inhibition of both GABA and the GABA(A) agonist. In contrast, the GABA(B) antagonist saclofen was without effect. These results reveal that GABA reduces the activated firing rate of inner hair cell afferents mediated by the GABA(A) receptor subtype.