title: mGluR6 deletion renders the TRPM1 channel in retina inactive.
abstract: In darkness, glutamate released from photoreceptors activates the metabotropic glutamate receptor 6 (mGluR6) on retinal ON bipolar cells. This activates the G protein G(o), which then closes transient receptor potential melastatin 1 (TRPM1) channels, leading to cells' hyperpolarization. It has been generally assumed that deleting mGluR6 would render the cascade inactive and the ON bipolar cells constitutively depolarized. Here we show that the rod bipolar cells in mGluR6-null mice were hyperpolarized. The slope conductance of the current-voltage curves and the current noise were smaller than in wild type. Furthermore, while in wild-type rod bipolar cells, TRPM1 could be activated by local application of capsaicin; in null cells, it did not. These results suggest that the TRPM1 channel in mGluR6-null rod bipolar cells is inactive. To explore the reason for this lack of activity, we tested if mGluR6 deletion affected expression of cascade components. Immunostaining for G protein subunit candidates Gα(o), Gβ(3), and Gγ(13) showed no significant changes in their expression or distribution. Immunostaining for TRPM1 in the dendritic tips was greatly reduced, but the channel was still present in the soma and primary dendrites of mGluR6-null bipolar cells, where a certain fraction of TRPM1 appears to localize to the plasma membrane. Consequently, the lack of TRPM1 activity in the null retina is unlikely to be due to failure of the channels to localize to the plasma membrane. We speculate that, to be constitutively active, TRPM1 channels in ON bipolar cells have to be in a complex, or perhaps require an unidentified factor.
authors: Joint Laboratory for Brain Function and Health, Jinan University and the University of Hong Kong, Jinan University, Guangzhou, China. xuying@jnu.edu.cn
authors: Ying
authors: Y
authors: Xu
authors: Anuradha
authors: A
authors: Dhingra
authors: Marie E
authors: ME
authors: Fina
authors: Chieko
authors: C
authors: Koike
authors: Takahisa
authors: T
authors: Furukawa
authors: Noga
authors: N
authors: Vardi
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D003712:Dendrites / Q000737:chemistry / Q000502:physiology; D017353:Gene Deletion; D020962:Heterotrimeric GTP-Binding Proteins / Q000032:analysis / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000502:physiology*; D051245:Retinal Bipolar Cells / Q000187:drug effects / Q000502:physiology*; D018689:Sensory System Agents / Q000494:pharmacology; D050053:TRPM Cation Channels / Q000032:analysis / Q000502:physiology*
chemical_list: D018094:Receptors, Metabotropic Glutamate; D018689:Sensory System Agents; D050053:TRPM Cation Channels; C116297:Trpm1 protein, mouse; C113897:metabotropic glutamate receptor 6; D020962:Heterotrimeric GTP-Binding Proteins; D002211:Capsaicin