TRPM1 is required for the depolarizing light response in retinal ON-bipolar cells
- 10 November 2009
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 106 (45), 19174-19178
- https://doi.org/10.1073/pnas.0908711106
Abstract
The ON pathway of the visual system, which detects increases in light intensity, is established at the first retinal synapse between photoreceptors and ON-bipolar cells. Photoreceptors hyperpolarize in response to light and reduce the rate of glutamate release, which in turn causes the depolarization of ON-bipolar cells. This ON-bipolar cell response is mediated by the metabotropic glutamate receptor, mGluR6, which controls the activity of a depolarizing current. Despite intensive research over the past two decades, the molecular identity of the channel that generates this depolarizing current has remained elusive. Here, we present evidence indicating that TRPM1 is necessary for the depolarizing light response of ON-bipolar cells, and further that TRPM1 is a component of the channel that generates this light response. Gene expression profiling revealed that TRPM1 is highly enriched in ON-bipolar cells. In situ hybridization experiments confirmed that TRPM1 mRNA is found in cells of the retinal inner nuclear layer, and immunofluorescent confocal microscopy showed that TRPM1 is localized in the dendrites of ON-bipolar cells in both mouse and macaque retina. The electroretinogram (ERG) of TRPM1-deficient (TRPM1(-/-)) mice had a normal a-wave, but no b-wave, indicating a loss of bipolar cell response. Finally, whole-cell patch-clamp recording from ON-bipolar cells in mouse retinal slices demonstrated that genetic deletion of TRPM1 abolished chemically simulated light responses from rod bipolar cells and dramatically altered the responses of cone ON-bipolar cells. Identification of TRPM1 as a mGluR6-coupled cation channel reveals a key step in vision, expands the role of the TRP channel family in sensory perception, and presents insights into the evolution of vertebrate vision.Keywords
This publication has 32 references indexed in Scilit:
- A Transient Receptor Potential-Like Channel Mediates Synaptic Transmission in Rod Bipolar CellsJournal of Neuroscience, 2009
- The developmental sequence of gene expression within the rod photoreceptor lineage in embryonic zebrafishDevelopmental Dynamics, 2008
- Differential Gene Expression of TRPM1, the Potential Cause of Congenital Stationary Night Blindness and Coat Spotting Patterns (LP) in the Appaloosa Horse (Equus caballus)Genetics, 2008
- Identification of molecular markers of bipolar cells in the murine retinaJournal of Comparative Neurology, 2008
- Evolution of the vertebrate eye: opsins, photoreceptors, retina and eye cupNature Reviews Neuroscience, 2007
- Syngeneic Schwann Cell Transplantation Preserves Vision in RCS Rat without ImmunosuppressionInvestigative Ophthalmology & Visual Science, 2007
- The light‐activated signaling pathway in SCN‐projecting rat retinal ganglion cellsEuropean Journal of Neuroscience, 2006
- Localization of nyctalopin in the mammalian retinaEuropean Journal of Neuroscience, 2006
- Expression and Up-Regulation of Alternatively Spliced Transcripts of Melastatin, a Melanoma Metastasis-Related Gene, in Human Melanoma CellsBiochemical and Biophysical Research Communications, 2000
- The Drosophila Light-Activated Conductance Is Composed of the Two Channels TRP and TRPLCell, 1996