TY - JOUR
T1 - RGS7 and -11 complexes accelerate the ON-bipolar cell light response
AU - Zhang, Jianmei
AU - Jeffrey, Brett G.
AU - Morgans, Catherine W.
AU - Burke, Neal S.
AU - Haley, Tammie L.
AU - Duvoisin, Robert M.
AU - Lane Brown, R.
PY - 2010/2
Y1 - 2010/2
N2 - Purpose. 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 α 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 (RGS7Δ/Δ), 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, Gβ5 and R9AP, were reduced in the outer plexiform layer of the RGS11-/- and RGS7Δ/Δ/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 RGS7Δ/Δ/RGS11-/- mice. The ERG measured from the RGS7Δ/Δ 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 RGS7Δ/Δ/RGS11-/- mouse compared with the WT. Conclusions. RGS11 plays a role in the deactivation of Gαo, which precedes activation of the depolarizing current in ONBPCs. RGS7 must also serve a role as changes in RGS7Δ/Δ/ RGS11-/- mice were greater than those in RGS11-/- mice.
AB - Purpose. 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 α 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 (RGS7Δ/Δ), 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, Gβ5 and R9AP, were reduced in the outer plexiform layer of the RGS11-/- and RGS7Δ/Δ/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 RGS7Δ/Δ/RGS11-/- mice. The ERG measured from the RGS7Δ/Δ 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 RGS7Δ/Δ/RGS11-/- mouse compared with the WT. Conclusions. RGS11 plays a role in the deactivation of Gαo, which precedes activation of the depolarizing current in ONBPCs. RGS7 must also serve a role as changes in RGS7Δ/Δ/ RGS11-/- mice were greater than those in RGS11-/- mice.
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U2 - 10.1167/iovs.09-4163
DO - 10.1167/iovs.09-4163
M3 - Article
C2 - 19797214
AN - SCOPUS:77449159788
SN - 0146-0404
VL - 51
SP - 1121
EP - 1129
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
IS - 2
ER -