Generation of Two Forms of the γ‐Aminobutyric Acid_A Receptor γ‐₂‐Subunit in Mice by Alternative Splicing

Abstract: γ‐Aminobutyric acid_A (GABA_A) receptors are multisubunit ligand‐gated ion channels which mediate neuronal inhibition by GABA and are composed of at least four subunit types (α, β, γ, and δ). The γ₂‐subunit appears to be essential for benzodiazepine modulation of GABA_A receptor function. In cloning murine γ₂‐subunits, we isolated cDNAs encoding forms of the subunit that differ by the insertion of eight amino acids, LLRMFSFK, in the major intracellular loop between proposed transmembrane domains M3 and M4. The two forms of the γ₂‐subunit are generated by alternative splicing, as demonstrated by cloning and partial sequencing of the corresponding gene. The eight‐amino‐acid insertion encodes a potential consensus serine phosphorylation site for protein kinase C. These results suggest a novel mechanism for the regulation of the GABA_A receptor by protein phosphorylation.