Modification of presynaptic CaM kinase II affinity for ATP in hippocampus after long term blockade of serotonin reuptake

Ca2+/calmodulin-dependent protein kinase II (CaMKII) is markedly enriched a t synapses, where it is involved in the control of synaptic transmission, t ransmitter release and synaptic plasticity, CaMKII has also been found to b e involved in the long-term action of antidepressants on post-receptor sign aling mechanisms, because monoamine reuptake inhibitors induced an increase in autophosphorylation and activity of the kinase in nerve terminals of hi ppocampus, To study whether changes in the amount of enzyme or kinetic chan ges, due to posttranslational modifications, are responsible for kinase act ivation in nerve terminals, alpha-CaMKII level and kinetic constants of the autophosphorylation reaction as a function of ATP concentration were measu red in presynaptic cytosol from hippocampus. Treatment with two serotonin r euptake inhibitors did not change the level of presynaptic kinase or the Vm ax of autophosphorylation reaction. Instead the Km of the kinase for ATP wa s decreased 2.8-fold with fluvoxamine and 3.5-fold with paroxetine, implyin g an increase in the affinity for ATP, This result represents the first fin ding of changes in kinetic constants of a major brain enzyme after treatmen t with antidepressant drugs, (C) 2000 Elsevier Science Inc, All rights rese rved.