Activation of Ca2+--calmodulin kinase II induces desensitization by background light in dogfish retinal 'on' bipolar cells.
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.
Shiells
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RA
Biophysics Unit, Physiology Department, University College London, Gower Street, London WC1E 6BT, UK.
Falk
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D000818:Animals; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004284:Dogfish / Q000378:metabolism*; D004789:Enzyme Activation; D066298:In Vitro Techniques; D008027:Light; D008564:Membrane Potentials / Q000187:drug effects / Q000528:radiation effects; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D018094:Receptors, Metabotropic Glutamate; D011493:Protein Kinase C; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium