CALCIUM CALMODULIN-DEPENDENT PROTEIN KINASE-II INCREASES GLUTAMATE AND NORADRENALINE RELEASE FROM SYNAPTOSOMES

A VARIETY of evidence indicates that calcium-dependent protein phosphorylation modulates the release of neurotransmitter from nerve terminals1-3. For instance, the injection of rat calcium/cal-modulin-dependent protein kinase II (Ca2+/CaM-dependent PK II) into the preterminal digit of the squid giant synapse leads to an increase in the release of a so-far unidentified neurotransmitter induced by presynaptic depolarization3,4. But until now, it has not been demonstrated that Ca2+/CaM-dependent PK II can also regulate neurotransmitter release in the vertebrate nervous system. Here we report that the introduction of Ca2+/CaM-depen-dent PK II, autoactivated5-8 by thiophosphorylation, into rat brain synaptosomes (isolated nerve terminals) increases the initial rate of induced release of two neurotransmitters, glutamate and noradrenaline. We also show that introduction of a selective peptidergic inhibitor of Ca2+/CaM-dependent PK II inhibits the initial rate of induced glutamate release. These results support the hypothesis3,9 that activation of Ca2+/CaM-dependent PK II in the nerve terminal removes a constraint on neurotransmitter release. © 1990 Nature Publishing Group.