Glycine-induced currents are insensitive to the glycine receptor alpha1 subunit-specific blocker, cyanotriphenylborate, in older circling mice.

摘要

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 alpha1 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 muM 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 muM 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 muM 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 alpha1 subunit-containing GlyRs in homozygous (cir/cir) mice.