A single amino acid exchange alters the pharmacology of neonatal rat glycine receptor subunit |
| |
Authors: | J Kuhse V Schmieden H Betz |
| |
Affiliation: | Zentrum für Molekulare Biologie Heidelberg, Universit?t Heidelberg, Federal Republic of Germany. |
| |
Abstract: | Agonist activation of the inhibitory glycine receptor (GlyR) in the adult vertebrate CNS is efficiently antagonized by the alkaloid strychnine. Here, we describe a novel rat GlyR alpha subunit cDNA (alpha 2*) that generates chloride channels of low strychnine sensitivity upon expression in Xenopus oocytes. Comparison with the highly homologous human alpha 2 polypeptide and site-directed mutagenesis identified a single amino acid exchange at position 167 that causes the altered pharmacology of alpha 2* receptors. Amplification by the polymerase chain reaction revealed a strong decrease in alpha 2* mRNA abundancy during postnatal spinal cord development. These data indicate that alpha 2* represents a ligand binding subunit of the previously identified neonatal GlyR isoform of low strychnine affinity. |
| |
Keywords: | |
|