GABAA-similar-receptor-subtypes mediate excitatory neurotransmission in the mammalian labyrinth: An experimental and clinical study

Abstract

The inhibitory action of GABA, mediated by the bicuculline-sensitive GABA_A- and the bicuculline-insensitive GABA_B-receptors in the central and peripheral nervous system is generally accepted. In contrast, the existence of an additional excitatory GABA-receptor in the labyrinth of warm blooded animals and in the corresponding structures in cold blooded animals is still controversial. Both the evident excitatory effects of GABA and the inhibitory effects of the GABA-antagonists bicuculline and Picrotoxin on the vestibular postsynaptic afferent activity are discussed as having either a direct influence on the afferents, mediated by a postsynaptic GABA-receptor, or an indirect presynaptic effect mediated by the efferents. With the aid of microiontophoretic techniques, we have demonstrated that, in cats, GABA acts quantitatively as an amplifier whereas the presynaptic activity, mediated by the efferent vestibular system, acts qualitatively as a modulator of the vestibular postsynaptic afferent activity. The GABA action is antagonized by bicuculline and it is assumed that a postsynaptic bicuculline-sensitive GABA-receptor is involved. Picrotoxin, a GABA-antagonist correspondent to bicuculline, suppresses induced labyrinthine nystagmus in healthy subjects and pathological labyrinthine (peripheral) spontaneous nystagmus in patients. Similarities in the direction and time courses of the action of the GABA-antagonists in humans and in cats suggest that in humans an excitatory bicuculline- and picrotoxin-sensitive GABA-receptor mediates the afferent vestibular information. The possibility of influencing this GABA_A similar-receptor-subtype by Picrotoxin in humans is the basis of a successful therapy programme for labyrinthine nystagmus and vertigo, including motion sickness.