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J. Zhang, C. W. Morgans, N. S. Burke, B. Jeffrey, R. M. Duvoisin, R. L. Brown; ON-Bipolar Cell Response Kinetics in RGS7/11-Deficient Mice. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1025.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal ON-bipolar cells depolarize in response to the light-induced reduction in synaptic glutamate. This response is mediated by deactivation of mGluR6 and Go, and subsequent activation of an unknown cation channel. The kinetics of most G-protein-based signaling cascades are limited by the rate of GTP hydrolysis, which is typically accelerated by interaction with a member of the RGS protein family. We have previously demonstrated that RGS7 and 11 are present in the dendritic tips of ON-bipolar cells, in conjunction with Gβ5, and their membrane anchor, R9AP. ON-bipolar cells respond to bright light stimuli within 50 ms, and we hypothesize that RGS7 and or 11 are required for rapid inactivation of Go. This hypothesis was tested by measuring the kinetics of chemically-simulated light responses in wt and RGS7/11-/- (DKO) mice.
ON-bipolar cell currents were recorded in the whole-cell patch-clamp mode in mouse retinal slices. Light responses were simulated chemically by bathing the slice in the mGluR6 activator, APB, followed by focal pressure application of the mGluR6 inhibitor, CPPG, to the ON-bipolar cell dendrites.
We measured the time lag between CPPG application and when the response reaches 10% of maximum, as well as the 10%-90% rise time. Preliminary results suggest that ON-bipolar cell responses were slightly delayed in the RGS7/11 DKO mice compared to wild-type littermates, however, the rise times were not significantly different.
The ON-bipolar cell response requires several steps prior to activation of the depolarizing cation current. These results suggest that the RGS7/11 proteins act at an early stage of this process, presumably by accelerating hydrolysis of GTP by Go, as a prelude to channel activation. Although genetic ablation of RGS7 and 11 delays channel activation slightly, it is still remarkably rapid, compared to the intrinsic rate of GTP hydrolysis by Go, which requires tens of seconds. Thus, it appears that either channel activation can be initiated prior to full Go deactivation, or there is yet another RGS protein involved in Go deactivation.
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