Abstract
Purpose: :
Bipolar cells exhibit different types of glutamate receptors, which lead to a separation of light signals into ON and OFF channels in the outer retina. OFF bipolar cells express ionotropic glutamate receptors (GluRs) of either AMPA- or kainate subtype, resulting in distinct response properties between bipolar cell types. In the mouse retina, GluR1 (AMPA) and GluR5 (kainate) are the predominant receptor subunits expressed by OFF bipolar cells. The aim of our study was to assign these GluR subunits to the five known mouse OFF bipolar cell types.
Methods: :
We applied immunohistochemistry to investigate the GluR expression pattern in experiments with wildtype and transgenic mouse retinas using GluR subunit specific antibodies. OFF Bipolar cells were labeled with cell-type specific antibodies or in transgenic mice. To identify functional glutamate receptors on bipolar cell dendrites, OFF bipolar cell types in retinal slices were voltage-clamped and AMPA-evoked currents were recorded. Specific GluR antagonists were used to isolate AMPA- and kainate-type GluR-mediated currents.
Results: :
GluR1 and GluR5 were not colocalized in the mouse retina. We provide evidence that GluR1 was colocalized with the dendritic tips of Type-1 cells. In agreement, AMPA-evoked currents in Type-1 bipolars were blocked by the AMPA-type antagonist Gyki-52466 confirming AMPA-type GluR expression in this cell type. Type-2 cell dendrites showed neither GluR1 nor GluR5 immunoreactivity. Interestingly, preliminary patch-clamp recordings suggest that Type-2 OFF bipolar cells express predominantly kainate-type GluRs. Type-3a, -3b, and -4 cells showed GluR5 immunoreactivity. However, we cannot rule out to date that Type-4 cells may co-express GluR1.
Conclusions: :
Our data shows a differentiated expression of GluR1 and GluR5 by mouse OFF bipolars. Such a distinct expression pattern forms the basis for parallel processing within the OFF channel of retinal signal transmission. None of the two analyzed GluR subunits could be assigned to Type-2 cells. Therefore, it remains to be elucidated which GluR subunit is expressed by this OFF bipolar cell.
Keywords: bipolar cells • excitatory amino acid receptors • signal transduction: pharmacology/physiology