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The Journal of Neuroscience, April 15, 1999, 19(8):2938-2944
The Metabotropic Receptor mGluR6 May Signal Through
Go, But Not Phosphodiesterase, in Retinal Bipolar Cells
Scott
Nawy
Departments of Ophthalmology and Visual Science, and Neuroscience,
Albert Einstein College of Medicine, Bronx, New York 10461
Bipolar cells are retinal interneurons that receive synaptic input
from photoreceptors. Glutamate, the photoreceptor transmitter, hyperpolarizes On bipolar cells by closing nonselective cation channels, an effect mediated by the metabotropic receptor mGluR6. Previous studies of mGluR6 transduction have suggested that the receptor couples to a phosphodiesterase (PDE) that preferentially hydrolyzes cGMP, and that cGMP directly gates the nonselective cation
channel. This hypothesis was tested by dialyzing On bipolar cells with
nonhydrolyzable analogs of cGMP. Whole-cell recordings were obtained
from On bipolar cells in slices of larval tiger salamander retina.
Surprisingly, On bipolar cells dialyzed with 8-(4-chlorophenylthio)-cyclic GMP (8-pCPT-cGMP), or 8-bromo-cyclic GMP
(8-Br-cGMP) responded normally to glutamate or
L-2-amino-4-phosphonobutyrate (L-APB). Response
amplitudes and kinetics were not significantly altered compared
with cells dialyzed with cGMP alone. Comparable results were obtained
with the PDE inhibitor 3-isobutyl-1-methyl-xanthine (IBMX) or with
8-pCPT-cGMP and IBMX together, indicating that PDE is not required for
mGluR6 signal transduction. Addition of the G-protein subunit
Go to the pipette solution suppressed the cation current
and occluded the glutamate response, whereas dialysis with
Gi or with transducin G had no significant effect
on either the cation current or the response. Dialysis of an antibody
directed against Go also reduced the glutamate response,
indicating a functional role for endogenous Go . These
results indicate that mGluR6 may signal through Go,
rather than a transducin-like G-protein.
Key words:
cGMP; 8-pCPT-cGMP; mGluR6; phosphodiesterase; retinal
bipolar cell; Go; phosphodiesterase
Copyright © 1999 Society for Neuroscience 0270-6474/99/1982938-07$05.00/0
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