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

1. Retinal 'on' bipolar cells possess a metabotropic glutamate receptor (mG luR6) linked to the control of a G-protein and cGMP-activated channels whic h functions to generate high synaptic amplification of rod signals, under d ark-adapted conditions. 2. Desensitization of 'on' bipolar cells is initiated by a rise in Ca2+ dur ing background light too weak to adapt rod photoreceptors. Desensitization could also be elicited by raising intra cellular Ca2+ above 1 muM. 3. In order to investigate the mechanism of desensitization, whole-cell cur rent responses to brief flashes and to steps of light mere obtained from vo ltage-damped '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 ce lls by dim background light and by 50 muM Ca2+, but also increased their fl ash sensitivity. 4. The substrate of phosphorylation by CaMKII is the 'on' bipolar cell cGMP -activated channels. Desensitization probably results from a reduction in t heir sensitivity to cGMP and a voltage-dependent decrease in their conducta nce. 5. A role for protein kinase C (PKC) in this process was excluded since act ivating PKC independently of Ca2+ with the phc,phorbol eater PMA failed to induce desensitization of 'on' bi-polar cells.