May 2007
Volume 48, Issue 13
ARVO Annual Meeting Abstract  |   May 2007
APB-Sensitive ON-Responses in ON-Bipolar Cells of GO1 Knockout Mice
Author Affiliations & Notes
  • H. Okawa
    University of Southern California, Los Angeles, California
    Neurosciences Graduate Program,
  • L. Birnbaumer
    NIEHS, Research Triangle Park, North Carolina
  • F. Rieke
    Physiology and Biophysics/HHMI, University of Washington, Seattle, Washington
  • A. P. Sampath
    University of Southern California, Los Angeles, California
    Physiology and Biophysics/Zilkha Neurogenetic Institute,
  • Footnotes
    Commercial Relationships H. Okawa, None; L. Birnbaumer, None; F. Rieke, None; A.P. Sampath, None.
  • Footnotes
    Support NIH Grant EY17606
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 4599. doi:
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      H. Okawa, L. Birnbaumer, F. Rieke, A. P. Sampath; APB-Sensitive ON-Responses in ON-Bipolar Cells of GO1 Knockout Mice. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4599.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose:: ON-bipolar cells receive glutamatagic inputs from photoreceptors. When glutamate release is reduced during light, cationic transduction channels open providing the ON response. A splice variant of a Go-protein α subunit (Go1α) is thought to be involved in the signaling pathway between mGluR6 and the transduction channels, however other components of the signaling pathway remain largely unknown. Our experiments suggest a role for a second G-protein in channel gating. To study light-evoked activity of this residual G-protein, we recorded membrane currents from bipolar cells in Go1α knockout (KO) mice.

Methods:: Whole-cell voltage clamp recordings (Vm = - 60 mV) were made from ON-bipolar cells in retinal slices (200 µm) from wild-type (WT), or Go1α KO mice. The slices were perfused with oxygenated Ames solutions at physiological temperatures (~35-37oC), and current responses were recorded following flashes from a blue LED (max ~ 470nm). The GTP analogues, GTP-γ-S and GDP- ß-S, were administered through recording pipettes, while the mGluR6 agonist APB was bath-applied.

Results:: GTP-γ-S (30µM) quickly eliminated flash responses in WT rod bipolar cells without opening transduction channels, consistent with Go1α leading to transduction channel closing. However, GDP-ß-S (500µM) also eliminated flash responses in WT rod bipolar cells without opening transduction channels, suggesting the default state of the transduction channels in the absence of G-protein activity is closed. These results suggest a second GDP- ß-S-sensitive mechanism (or G-protein) may be involved in transduction channel opening, thus we recorded flash responses from KO ON-bipolar cells. In KO mice we surprisingly found small residual ON-responses with kinetics similar to WT responses. The ON-responses were totally and reversibly abolished by APB (8µM). OFF-responses recorded from OFF-bipolar cells in the same slices were insensitive to APB, suggesting the specificity of APBs action on mGluR6 in ON-bipolar dendrites.

Conclusions:: The mGluR6 signaling pathway in ON-bipolar cells can continue to generate ON responses in the absence of Go1α. However, the size of these residual ON-responses is smaller than WT, making the functional significance of the possible second pathway unclear. A possible second pathway may involve the less efficacious mGluR6 coupling through Go2α, but such activity has not been observed in ERG recordings from Go1α KO mice.

Keywords: retina: distal (photoreceptors, horizontal cells, bipolar cells) • bipolar cells • synapse 

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