PERSISTENT GABAA/C RESPONSES TO GABAZINE, TAURINE AND BETA-ALANINE IN RAT HYPOGLOSSAL MOTONEURONS

In hypoglossal motoneurons, a sustained anionic current, sensitive to a blocker of rho-containing GABA receptors, (1,2,5,6-tetrahydropyridin-4-yl) methylphosphinic acid (TPMPA) and insensitive to bicuculline, was previously shown to be activated by gabazine. In order to better characterize the receptors involved, the sensitivity of this atypical response to pentobarbital (30 mu M), allopregnanolone (0.3 mu M) and midazolam (0.5 mu M) was first investigated. Pentobarbital potentiated the response, whereas the steroid and the benzodiazepine were ineffective. The results indicate the involvement of hybrid heteromeric receptors, including at least a GABA receptor rho subunit and a gamma subunit, accounting for the pentobarbital-sensitivity. The effects of the endogenous beta amino acids, taurine and beta-alanine, which are released under various pathological conditions and show neuroprotective properties, were then studied. In the presence of the glycine receptor blocker strychnine (1 mu M), both taurine (0.3-1 mM) and beta-alanine (0.3 mM) activated sustained anionic currents, which were partly blocked by TPMPA (100 mu M). Thus, both beta amino acids activated rho-containing GABA receptors in hypoglossal motoneurons. Bicuculline (20 mu M) reduced responses to taurine and beta-alanine, but small sustained responses persisted in the presence of both strychnine and bicuculline. Responses to beta-alanine were slightly increased by allopregnanolone, indicating a contribution of the bicuculline- and neurosteroid-sensitive GABA(A) receptors underlying tonic inhibition in these motoneurons. Since sustained activation of anionic channels inhibits most mature principal neurons, the rho-containing GABA receptors permanently activated by taurine and beta-alanine might contribute to some of their neuroprotective properties under damaging overexcitatory situations. (C) 2016 IBRO. Published by Elsevier Ltd. All rights reserved.