Comparison of glycine and GABA actions on the zebrafish homomeric glycine receptor

Glycine and GABA can be co-released from the same presynaptic terminals and in lower vertebrates they can activate the same glycine receptors (GlyRs). Thus we examined the effects of these two inhibitory transmitters on the homomeric GlyRs formed by the αZ1 subunit, of the zebrafish using two expression systems: Xenopus oocytes and the human BOSC 23 cell line. The apparent affinity (EC 50 ) of αZ1 for these neurotransmitters was highly variable. In Xenopus oocytes the EC 50 ranged from 37 to 360 μ m (mean ± s.d. EC 50 116 ± 75 μ m , n = 83) for glycine and from 8 to 120 mM (mean EC 50 40 ± 30 mM, n = 37) for GABA. In BOSC cells the EC 50 varied from 9 to 92 μ m (mean EC 50 33 ± 17 μ m , n = 19) and from 0.7 to 19.1 mM (mean EC 50 4.9 ± 4.7 mM, n = 29) for glycine and GABA, respectively. GABA activated αZ1 GlyRs either as a weak or full agonist: its efficacy (defined as I max, GABA / I max, Gly ) was related to EC 50 by an exponential relationship. A linear relationship was observed between EC 50 values for GABA and glycine. In outside-out patches, GABA and glycine activated αZ1 with identical single-channel conductances (85-100 pS), but with different kinetics and marked effect of concentration on burst duration for glycine only. In outside-out patches deactivation time constants were concentration dependent for glycine, but not for GABA. Our data demonstrate that the kinetics of glycine and GABA interactions with αZ1 are different and that they determine the properties of these neurotransmitter actions on the GlyR.