PHYSIOLOGY AND PHARMACOLOGY OF NATIVE GLYCINE RECEPTORS IN DEVELOPINGRAT AUDITORY BRAIN-STEM NEURONS

Glycinergic neurotransmission is mediated via inhibitory glycine recep tors (GlyRs) which are heterogeneous during development. Electrophysio logical studies performed on recombinant GlyRs have identified differe nt pharmacological properties and attributed them to differences in th eir subunit composition. Here, we report on age-related changes in the response properties of native GlyRs in the mammalian brain. Whole-cel l patch-clamp recordings were obtained from neurons of the medial nucl eus of the trapezoid body (MNTB), a major relay station in the mammali an auditory brainstem. Experiments were performed in acute medullary s lices of rats between postnatal day (P) 1 and P15, a period during whi ch synapse maturation occurs. Glycine-induced currents were present th roughout the period under investigation and displayed age-related modi fications in their amplitude, kinetic characteristics, and sensitivity to drugs. Current amplitudes and GlyR desensitization behavior increa sed with age. The alpha(1) subunit-specific GlyR antagonist cyanotriph enylborate (CTB) was barely effective in reducing glycine-induced curr ents during the first few postnatal days, yet a significant increase o f the inhibitory effect occurred after the first postnatal week. This finding indicates that alpha(1) subunit-containing GlyRs become expres sed only postnatally in the MNTB. Picrotoxin, which most effectively b locks recombinant alpha(2)-homooligomers, reduced glycine-induced curr ents in neonatal MNTB neurons, suggesting that alpha(2)-homooligomers may form native GlyR isoforms. Our results show that the physiology an d pharmacology of GlyRs in the auditory brainstem underlie age-related changes which are most probably produced through a replacement of ''n eonatal'' alpha(2) subunits with ''adult'' alpha(1) subunits. (C) 1997 Elsevier Science B.V.