Background: Functional GlyR␣1 receptors can be reconstituted from nonfunctional subunit domains. Results: GlyR␣3 and GABA A R1 rescues are less efficient with the alternative splicing cassette in the TM3-4 loop of GlyR␣3 responsible for desensitization and rescue efficiency. Conclusion: Desensitization of GlyR␣3 requires nondisrupted intracellular domains. Significance: Independent domain reconstitution does not always recapitulate the full functional properties of receptors.

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