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Glutamate released onto retinal ON bipolar neurons binds to a metabotropic receptor to activate a heterotrimeric G-protein (Go) that ultimately closes a nonspecific cation channel. Signaling requires the α subunit (Gαo), but its effector is unknown. Because Gαo is transcribed into two splice variants (αo1 and αo2) 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 αo1 and αo2 are expressed by ON bipolar cells but that αo1 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 αo1 but not αo2. Thus, the light response of the ON bipolar cell is probably carried by its strongly expressed splice variant, Gαo1.

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

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