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Melissa Rampino, Scott Nawy; Role of PKCα in Modulating TRPM1 function in Retinal Rod Bipolar Cells. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4808.
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© ARVO (1962-2015); The Authors (2016-present)
Light onset information in the outer retina is propagated via the mGluR6 receptor/TRPM1 channel transduction pathway in ON bipolar cells. In contrast to the cone-driven ON pathway, the rod pathway detects light stimuli as dim as a single photon, and therefore is a highly sensitive channel for conveying light information. Furthermore, rod, but not cone-driven bipolar cells strongly express the kinase PKCα. Here we explore the possibility that PKCα regulates the performance of the mGluR6/TRPM1 complex in rod bipolar cells.
Patch-clamp recordings were performed in rod bipolar cells in acute mouse retinal slices. Pharmacological simulation of dark and light conditions was used to mimic light responses of rod bipolar cells under voltage clamp conditions. The simulated light response was elicited by displacing 4 µM bath-applied L-AP4 with 500 ms puffs of the mGluR antagonist LY351495 at a concentration of 500 µM. Rod- and cone-driven bipolar cells were distinguished by morphological criteria following filling with Alexa 488.
We found that the unique expression of PKCα by rod bipolar cells (RBCs) contributes to the high degree of sensitivity of the rod-RBC synapse. Both pharmacological inhibition and genetic deletion of PKCα in mice resulted in an approximately 20% smaller peak amplitude of the simulated light responses as compared to wild type. This was found to be true over a range of stimulus intensities. Addition of the PKC activator OAG potentiated the simulated light response in RBCs by approximately 116% in wild type mice, but not in PKCα(-/-) mice. On the other hand, OAG had no effect on the simulated light response of cone-driven bipolar cells in either wild type or PKCα(-/-) mice.
Activation of PKCα in RBCs amplifies TRPM1 current at the rod-RBC synapse, thereby increasing the sensitivity of transmission of dim light information.
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