Activation of Ca2+--calmodulin kinase II induces desensitization by background light in dogfish retinal 'on' bipolar cells

J Physiol. 2000 Oct 15;528 Pt 2(Pt 2):327-38. doi: 10.1111/j.1469-7793.2000.00327.x.


Retinal 'on' bipolar cells possess a metabotropic glutamate receptor (mGluR6) linked to the control of a G-protein and cGMP-activated channels which functions to generate high synaptic amplification of rod signals under dark-adapted conditions. Desensitization of 'on' bipolar cells is initiated by a rise in Ca2+ during background light too weak to adapt rod photoreceptors. Desensitization could also be elicited by raising intracellular Ca2+ above 1 microM. In order to investigate the mechanism of desensitization, whole-cell current responses to brief flashes and to steps of light were obtained from voltage-clamped 'on' bipolar cells in dark-adapted dogfish retinal slices. The inclusion of Ca2+-calmodulin kinase II (CaMKII) inhibitor peptides in the patch pipette solutions not only blocked desensitization of 'on' bipolar cells by dim background light and by 50 microM Ca2+, but also increased their flash sensitivity. The substrate of phosphorylation by CaMKII is the 'on' bipolar cell cGMP-activated channels. Desensitization probably results from a reduction in their sensitivity to cGMP and a voltage-dependent decrease in their conductance. A role for protein kinase C (PKC) in this process was excluded since activating PKC independently of Ca2+ with the phorbol ester PMA failed to induce desensitization of 'on' bipolar cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Dogfish / metabolism*
  • Enzyme Activation
  • In Vitro Techniques
  • Light
  • Membrane Potentials / drug effects
  • Membrane Potentials / radiation effects
  • Patch-Clamp Techniques
  • Protein Kinase C / metabolism
  • Receptors, Metabotropic Glutamate / metabolism
  • Retina / cytology
  • Retina / metabolism*
  • Retina / radiation effects*
  • Tetradecanoylphorbol Acetate / pharmacology


  • Receptors, Metabotropic Glutamate
  • Protein Kinase C
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Tetradecanoylphorbol Acetate
  • Calcium