The mutant allele GLRA1 (P250T) of the glycine receptor alpha1 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 alpha1(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 EC(50) values. 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.