Persistent GABAA/C responses to gabazine, taurine and beta-alanine in rat hypoglossal motoneurons

- Gabazine activates a bicuculline-resistant and TPMPA-sensitive Cl− current in HMs.
- Pentobarbital potentiates this response whereas allopregnanolone and midazolam do not.
- The receptors involved are likely hybrid GABA receptors including ρ and γ subunits.
- β amino acids activate strychnine-resistant, TPMPA-sensitive, sustained Cl− currents.
- The resulting sustained inhibition should contribute to neuroprotection by taurine.

In hypoglossal motoneurons, a sustained anionic current, sensitive to a blocker of ρ-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 μM), allopregnanolone (0.3 μM) and midazolam (0.5 μM) 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 ρ subunit and a γ subunit, accounting for the pentobarbital-sensitivity. The effects of the endogenous β amino acids, taurine and β-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 μM), both taurine (0.3-1 mM) and β-alanine (0.3 mM) activated sustained anionic currents, which were partly blocked by TPMPA (100 μM). Thus, both β amino acids activated ρ-containing GABA receptors in hypoglossal motoneurons. Bicuculline (20 μM) reduced responses to taurine and β-alanine, but small sustained responses persisted in the presence of both strychnine and bicuculline. Responses to β-alanine were slightly increased by allopregnanolone, indicating a contribution of the bicuculline- and neurosteroid-sensitive GABAA receptors underlying tonic inhibition in these motoneurons. Since sustained activation of anionic channels inhibits most mature principal neurons, the ρ-containing GABA receptors permanently activated by taurine and β-alanine might contribute to some of their neuroprotective properties under damaging overexcitatory situations.