Suppression by glutamate of cGMP-activated conductance in retinal bipolar cells

Nature. 1990 Jul 19;346(6281):269-71. doi: 10.1038/346269a0.


Depolarizing bipolar cells (DBCs) of the retina are the only neurons in the vertebrate central nervous system known to be hyperpolarized by the neurotransmitter glutamate. Both glutamate and its analogue L-2-amino-4-phosphonobutyrate (APB) hyperpolarize DBCs by decreasing membrane conductance. Furthermore, glutamate responses in DBCs slowly decrease during whole-cell recording, suggesting that the response involves a second messenger system. Here we report that intracellular cyclic GMP or GTP activates a membrane conductance that is suppressed by APB, resulting in an enhanced APB response. In the presence of GTP-gamma-S, APB causes an irreversible suppression of the conductance. Inhibitors of G-protein activation or phosphodiesterase activity decrease the APB response. Thus, the DBC glutamate receptor seems to close ion channels by increasing the rate of cGMP hydrolysis by a G protein-mediated process that is strikingly similar to light transduction in photoreceptors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 1-Methyl-3-isobutylxanthine / pharmacology
  • Aminobutyrates / pharmacology
  • Animals
  • Cell Membrane / drug effects
  • Cell Membrane / physiology
  • Cyclic GMP / pharmacology*
  • Electric Conductivity
  • GTP-Binding Proteins / physiology
  • Glutamates / pharmacology*
  • Glutamic Acid
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Guanosine Triphosphate / analogs & derivatives
  • Guanosine Triphosphate / pharmacology
  • Photoreceptor Cells / physiology
  • Receptors, Glutamate
  • Receptors, Neurotransmitter / physiology
  • Retina / physiology*
  • Second Messenger Systems
  • Thionucleotides / pharmacology
  • Urodela


  • Aminobutyrates
  • Glutamates
  • Receptors, Glutamate
  • Receptors, Neurotransmitter
  • Thionucleotides
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Glutamic Acid
  • Guanosine Triphosphate
  • GTP-Binding Proteins
  • Cyclic GMP
  • 2-amino-4-phosphonobutyric acid
  • 1-Methyl-3-isobutylxanthine