CLONING AND FUNCTIONAL EXPRESSION OF ALTERNATIVE SPLICED VARIANTS OF THE RHO-1 GAMMA-AMINOBUTYRATE RECEPTOR

The rho 1 gamma-aminobutyrate receptor (GABA(rho 1)) is expressed pred ominantly in the retina and forms homomeric GABA-gated Cl- channels th at are clearly different from the multisubunit GABAA receptors, In con trast to these, GABA(A) receptors desensitize very little and are not blocked by bicuculline, In addition to GABA(rho 1), two new variants w ere identified in human retina cDNA libraries, Cloning and sequence an alysis showed that both variants contain large deletions in the putati ve extracellular domain of the receptor, These deletions extend from a common 5' site to different 3' sites, The cDNA with the largest delet ion, named GABA(rho 1)Delta 450, contains a complete ORF identical to that of GABA(rho 1) but missing 450 nt, This cDNA encodes a protein of 323 aa, identical to the GABA(rho 1), but has a deletion of 150 aa in the amino-terminal extracellular domain, GABA(rho 1)Delta 450 mRNA in jected into Xenopus oocytes did not produce functional GABA receptors, The second GABA(rho 1) variant (GABA(rho 1)Delta 51) contains a 51-nt deletion, In Xenopus oocytes, GABA(rho 1)Delta 51 led to the expressi on of GABA receptors that had the essential GABA(rho 1) characteristic s of low desensitization and bicuculline resistance. Therefore, altern ative splicing increases the coding potential of this gene family expr essed In the human retina, but the functional diversity created by the alternative spliced forms is still not understood.