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

Biochem Biophys Res Commun. 2011 Feb 11;405(2):157-61. doi: 10.1016/j.bbrc.2010.12.127. Epub 2011 Jan 6.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Borates / pharmacology*
  • Deafness / congenital
  • Deafness / physiopathology*
  • Disease Models, Animal
  • GABA Antagonists / pharmacology
  • Glycine / pharmacology*
  • Homozygote
  • Mice
  • Mice, Mutant Strains
  • Picrotoxin / pharmacology
  • Receptors, Glycine / antagonists & inhibitors*
  • Receptors, Glycine / physiology
  • Synapses / drug effects

Substances

  • Borates
  • GABA Antagonists
  • Receptors, Glycine
  • Picrotoxin
  • cyanotriphenylborate
  • Glycine