Molecular mechanisms of neuronal excitability: possible involvement of CaM kinase II in seizure activity.

A type II calmodulin-dependent protein kinase (CaM kinase II) has been characterized in the synaptic region and may mediate some of the effects of Ca2+ on neuronal excitability. The activity of CaM kinase II is inhibited by anticonvulsant compounds and may be the molecular basis of their neuro-modulatory effects. The direct injection of purified CaM kinase II into invertebrate neurons has demonstrated that this kinase can directly alter specific ion conductances and neuronal activity. A long-lasting decrease in CaM kinase II activity is associated with septal kindling, an experimental model of epilepsy and long-term memory. In summary, CaM kinase II appears to be a central mediator of the effects of Ca2+ on neuronal function. Further investigation of this enzyme and its effects on neuronal activity may provide a molecular insight into an endogenous mechanism for modulating some of the effects of Ca2+ on neuronal excitability and may increase our understanding of the complex regulatory mechanisms that underlie the pathogenesis of seizure discharge and its regulation by anticonvulsant compounds.