RGS7 and -11 complexes accelerate the ON-bipolar cell light response.
OBJECTIVE
The retinal ON-bipolar cell (ON-BPC) light response is initiated upon deactivation of the metabotropic glutamate receptor mGluR6 and the G protein Go. G protein-based signaling cascades are typically accelerated by interaction of the G protein alpha subunit with a member of the regulator of G protein signaling (RGS) protein family. The goal of this study was to determine whether RGS7 and/or -11 serve this function in retinal ON-BPCs.


METHODS
Retinas from mice lacking RGS11 (RGS11(-/-)), or with a deletion mutation in RGS7 (RGS7(Delta/Delta)), or both, were compared to wild-type (WT) by immunofluorescence confocal microscopy. The retinal light response was measured with the electroretinogram (ERG). The kinetics of simulated light responses from individual rod bipolar cells were recorded by whole-cell patch-clamp electrophysiology.


RESULTS
Levels of the R7 RGS interaction partners, Gbeta5 and R9AP, were reduced in the outer plexiform layer of the RGS11(-/-) and RGS7(Delta/Delta)/RGS11(-/-) mice. ERG recordings demonstrated a delay in the rising phase of the ERG b-wave, larger photopic b-wave amplitudes, and increased scotopic threshold response sensitivity in the RGS11(-/-) and RGS7(Delta/Delta)/RGS11(-/-) mice. The ERG measured from the RGS7(Delta/Delta) retina was normal. Patch-clamp recordings of chemically simulated light responses of rod BPCs revealed a 25-ms delay in the onset of the ON-BPC response in the RGS7(Delta/Delta)/RGS11(-/-) mouse compared with the WT.


CONCLUSIONS
RGS11 plays a role in the deactivation of Galphao, which precedes activation of the depolarizing current in ON-BPCs. RGS7 must also serve a role as changes in RGS7(Delta/Delta)/RGS11(-/-) mice were greater than those in RGS11(-/-) mice.
Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, Washington State University, Pullman, Washington, USA.
Jianmei
J
Zhang
Brett G
BG
Jeffrey
Catherine W
CW
Morgans
Neal S
NS
Burke
Tammie L
TL
Haley
Robert M
RM
Duvoisin
R Lane
RL
Brown
D000818:Animals; D015153:Blotting, Western; D004594:Electrophysiology; D004596:Electroretinography; D005838:Genotype; D006160:Guanosine Triphosphate / Q000378:metabolism; D006868:Hydrolysis; D007150:Immunohistochemistry; D008027:Light; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D018408:Patch-Clamp Techniques; D010775:Photic Stimulation; D020710:RGS Proteins / Q000502:physiology*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D051245:Retinal Bipolar Cells / Q000378:metabolism / Q000528:radiation effects*; D015398:Signal Transduction / Q000502:physiology*
D020710:RGS Proteins; D018094:Receptors, Metabotropic Glutamate; C485693:Rgs11 protein, mouse; C492038:Rgs7 protein, mouse; C113897:metabotropic glutamate receptor 6; D006160:Guanosine Triphosphate