Glycine-induced currents are insensitive to the glycine receptor α1 subunit-specific blocker, cyanotriphenylborate, in older circling mice

The pharmacologic characteristics of glycine receptors (GlyRs) in the lateral superior olive (LSO) of circling mice, animal model for inherited deafness, were investigated using a GlyR α1 subunit-specific receptor blocker (cyanotriphenylborate [CTB]). There was a statistically significant age-dependent increase in the antagonistic effect of CTB in heterozygous (+/cir) mice. In postnatal (P)0–P3 heterozygous (+/cir) mice, glycine currents evoked by glycine puffs were reduced to 20.4 ± 2.6, 37.1 ± 3.1, and 63.9 ± 2.5% at 0.1, 1, and 10 μM CTB (n = 13) compared to controls, while the glycine currents were reduced to 22.3 ± 3.5, 52.9 ± 4.1, and 78.3 ± 3.5% at 0.1, 1, and 10 μM CTB (n = 7) in P8–P12 heterozygous (+/cir) mice. In contrast, the antagonistic effect of CTB was not strong and even less than that of younger animals in older homozygous (cir/cir) mice. In P0–P3 homozygous (cir/cir) mice, the extent of inhibition was 20.2 ± 3.7, 37.8 ± 4.3, and 66.8 ± 4.2% at 0.1, 1, and 10 μM CTB (n = 6) compared to controls, while the extent of inhibition was 18.7 ± 2.4, 28.1 ± 3.9, and 39.1 ± 8.2% (n = 6) in P8–P12 homozygous (cir/cir) mice. The age-dependent decrease in the antagonistic effect of CTB indicates the abnormal development of the α1 subunit-containing GlyRs in homozygous (cir/cir) mice.

Research highlights► Glycine-induced currents are slower in inactivation in older circling mice. ► Glycine-induced currents are insensitive to CTB in older circling mice. ► Antagonistic effects of PTX are similar in younger and older circling mice.