The metabotropic receptor mGluR6 may signal through G(o), but not phosphodiesterase, in retinal bipolar cells

Scott Nawy

Research output: Contribution to journalArticle

118 Scopus citations

Abstract

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 G(o)α to the pipette solution suppressed the cation current and occluded the glutamate response, whereas dialysis with G(i)α or with transducin Gβγ had no significant effect on either the cation current or the response. Dialysis of an antibody directed against G(o)α also reduced the glutamate response, indicating a functional role for endogenous G(o)α. These results indicate that mGluR6 may signal through G(o), rather than a transducin-like G-protein.

Original languageEnglish (US)
Pages (from-to)2938-2944
Number of pages7
JournalJournal of Neuroscience
Volume19
Issue number8
StatePublished - Apr 15 1999

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Keywords

  • 8-pCPT-cGMP
  • G(o)
  • Phosphodiesterase
  • Retinal bipolar cell
  • cGMP
  • mGluR6

ASJC Scopus subject areas

  • Neuroscience(all)

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