The mutant allele GLRA1(P250T) of the glycine receptor α1 subunit gene underlies a dominant form of the human neurological disorder, hyperekplexia. The encoded substitution, residing within the short intracellular TM1-2 loop, leads to dramatically accelerated desensitization and reduced apparent ligand affinity. Here, dominant negative effects of the α1(P250T) subunit on receptor function were studied in a recombinant system. Coexpression of varying ratios of wildtype and mutant cDNA resulted in intermediate desensitization time constants and EC50values. The gradual transition of current response properties indicated random coassembly of receptor subunits. Different from the dominant trait of clinical hyperekplexia associated with GLRA1(P250T), wildtype subunits dominated the functional properties of mixed receptor complexes in the recombinant system. © 2002 Elsevier Science Ireland Ltd. All rights reserved.
Breitinger, H. G., & Becker, C. M. (2002). Statistical coassembly of glycine receptor α1 wildtype and the hyperekplexia mutant α1(P250T) in HEK 293 cells: Impaired channel function is not dominant in the recombinant system. Neuroscience Letters, 331(1), 21–24. https://doi.org/10.1016/S0304-3940(02)00773-5