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J. Snellman, S. Nawy; cGMP–Dependent Kinase Mediated Changes in Rod Bipolar Cell Sensitivity Are Transmitted to AII Amacrine Cells of the Inner Retina . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3458.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: We have previously shown that cGMP–dependent kinase (cGK) changes the efficacy with which glutamate activates the mGluR6 cascade. Stimulation of cGK results in a reduced ability of the receptor to close its G–protein coupled channel, making it more likely for small changes in glutamate release to be detected. This is especially important during conditions of high transmitter release, such as darkness, when increased sensitivity is desirable. Here, we have investigated whether our previously reported changes in rod bipolar cell (RBC) sensitivity, mediated by cGK, are passed on to the inner retina. Methods: Mouse retinal slices were bathed in saturating concentrations of the mGluR6 agonist L–AP4 to mimic darkness, and light flashes were simulated by focal puffs of the antagonist CPPG onto the RBC dendrites. Responses were recorded in AII amacrine cells voltage clamped to –60 mV. Results: Brief puffs (8–50 ms) of CPPG onto RBC dendrites that elicited small depolarizations in RBCs often failed to elicit a response in the postsynaptic AII. Presumably these depolarizations were insufficient to induce transmitter release from the RBC synaptic terminals. After bath application of the membrane permeant cGMP analog Sp–8–Br–PET–cGMPS (cGMPmp), brief puffs of CPPG reliably elicited EPSCs in AIIs. However, cGMPmp did not affect the size of the maximum response, elicited by long puffs. To quantify this effect of cGMP on the AII EPSC, we plotted the dose–response function for CPPG before and after cGMP application. The function was shifted to the left by cGMPmp, decreasing the puff length required to elicit half–maximal EPSC in the AII from 90.5 ms to 42.0 ms, consistent with our previously reported findings in the RBC. Intracellular dialysis of the AII with cGMP had no effect on the EPSC, suggesting that the primary target of the membrane permeant cGMP analog was the RBC. Conclusions: Here, we report that cGK mediated potentiation of small EPSCs in the RBC is carried on to AII amacrine cells in the inner retina. Comparison of the dose response functions of RBCs and AIIs pose the possibility that cGMP may bring the RBC past threshold for transmitter release, allowing AII EPSCs to develop in response to previously sub–threshold stimulation. Our results indicate that activation of cGK in RBCs may be an important mechanism for adjusting retinal sensitivity to light throughout the On pathway.
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