Glycine receptors containing the alpha 4 subunit in the embryonic sympathetic nervous system, spinal cord and male genital ridge

Inhibitory glycine receptors (GlyRs) are known to mediate postsynaptic inhi bition in spinal cord, brain stem and some higher brain regions. Several de velopmentally and regionally regulated GlyR isoforms exist, which result fr om a differential expression of the GlyR alpha (alpha 1-alpha 4) and beta s ubunit genes. Currently, very little is known about GlyRs containing the al pha 4 subunit, whose existence was predicted from a partial genomic sequenc e. Here, we describe the isolation of complementary DNA (cDNA) sequences fo r the mouse and chick GlyR alpha 4 subunits. We show that a mouse GlyR alph a 4 subunit full-length cDNA directs the formation of functional homo-oligo meric strychnine-sensitive GlyRs in Xenopus laevis oocytes and mammalian ce lls, and that these resemble GlyRs composed of the alpha 1 subunit in pharm acological profile and single-channel properties. In situ hybridization rev eals high levels of GlyR alpha 4 subunit transcripts in the embryonic (E13) chick spinal cord, lumbosacral sympathetic ganglia and dorsal root ganglia . The avian GlyR alpha 4 subunit gene also shows male-specific expression i n the developing genital ridge. The pharmacological profile of alpha 4 subu nit-containing receptors and deduced location of the avian GlyR alpha 4 sub unit are consistent with it being a component of the embryonic excitatory G lyRs previously identified in sympathetic neurons. Our data also suggest a novel role for GlyRs in the maturation of reproductive organs.