Light Response of Retinal ON Bipolar Cells Requires a Specific Splice Variant of Gα_o

Glutamate released onto retinal ON bipolar neurons binds to a metabotropic receptor to activate a heterotrimeric G-protein (G_o) that ultimately closes a nonspecific cation channel. Signaling requires the α subunit (Gα_o), but its effector is unknown. Because Gα _o is transcribed into two splice variants (α_o1 and α_o2) that differ in the key GTPase domain, the next step in elucidating this pathway was to determine which splice variant carries the signal. Here we show by reverse transcription-PCR and Western blots that retina expresses both splice variants. Furthermore, in situ hybridization and immunostaining on mouse retina deficient in one splice variant or the other show that both α_o1 and α_o2 are expressed by ON bipolar cells but that α_o1 is much more abundant. Finally, electroretinography performed on mice deficient for one splice variant or the other shows that the positive b-wave (response of ON bipolar cells to rod and cone input) requires α_o1 but not α_o2. Thus, the light response of the ON bipolar cell is probably carried by its strongly expressed splice variant, Gα_o1.