Alternative transcripts of the GABA_A receptor ε subunit in human and rat

In both human and rat tissues, complex patterns of transcripts are derived from the genes that encode the γ-aminobutyric acid (GABA)_A receptor ε subunit. An ε subunit transcript (∼3.6 kb) is expressed at relatively high levels in regions of the human brain and heart, but is not detected in most other major tissues. The encoded human ε subunit (ε_h) confers distinctive properties to receptors into which it assembles. A distinct transcript of the gene (6.2 kb) is expressed abundantly in a variety of human tissues. This alternative transcript (ET2) appears to originate from within the ε subunit gene. It is possible that this transcript encodes a truncated subunit (ε_hS), containing all of the transmembrane and intracellular domains. However, a combination of biochemical and electrophysiological analyses does not support this hypothesis. A distinct transcript of the ε subunit gene, encoding a large extracellular pro/glx domain, is expressed abundantly in rat and mouse brain. Functional analyses also failed to provide evidence for incorporation of this subunit (ε_rL) into recombinant receptors. However, a shorter rat ε subunit (ε_r), which lacks the pro/glx domain, conferred ε_h-like properties to recombinant receptors, providing evidence for a functional rat ε subunit. In common with its human orthologue, incorporation of the ε_r subunit into recombinant GABA_A receptors confers several distinctive properties, including a reduced modulation by the anesthetic propofol and the appearance of spontaneous current.