Kinetic model for phototransduction and G-protein enzyme cascade: understanding quantal bumps during inhibition of CaM-KII or PP2B.
We utilize a computer model derived directly from the phototransductive enzyme cascade involving rhodopsin (R), G-proteins (G) and ultimately the membrane channels. In photoreceptors, single photons activate single rhodopsin molecules (R*), resulting in the production of quantal bumps. A CaM-KII inhibitor may inhibit whereas calcineurin (PP2B) inhibitors may augment arrestin activity. Arrestin is known to inactivate R*. We voltage-clamped and digitized quantal bumps for comparison with the kinetic model and simulations. Inhibitors of CaM-KII and PP2B produce results consistent with altering arrestin activity. In sum, we have succeeded in constructing a mathematical description of the phototransduction cascade that is biochemically derived and useful in interpreting results.
Kass
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Department of Zoology, University of Maine, Orono 04469-1221, USA. LKASS@physics.uoguelph.ca
Bray
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D000818:Animals; D019703:Calcineurin; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002148:Calmodulin-Binding Proteins / Q000378:metabolism*; D003198:Computer Simulation; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006737:Horseshoe Crabs; D008954:Models, Biological; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors; D014785:Vision, Ocular
D002148:Calmodulin-Binding Proteins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; D010744:Phosphoric Monoester Hydrolases; D019204:GTP-Binding Proteins