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Two cDNAs encoding novel GABAA receptor subunits were isolated from a rat brain library. These subunits, y2 and 6, share approximately 35% sequence identity with a and R subunits and form functional GABA-gated chloride channels when expressed alone in vitro. The y2 subunit is the rat homolog of the human y2 subunit recently shown to be important for benzodiazepine pharmacology. Cellular localization of the mRNAs encoding the y2 and 6 subunits in rat brain revealed that largely distinct neuronal subpopulations express the two subunits. The 6 subunit distribution resembles that of the high affinity GABAA receptor labeled with [sH] muscimol; the 72 subunit distribution resembles that of GARA, &enzodiazepine receptors labeled with [3H] flunitrazepam. These findings have implications for the composition of two different GABAA receptor subtypes and for information processing in networks using GABA for …