A role for calcium/calmodulin-dependent protein kinase in mediating synaptic modulation by a neuropeptide.

The crayfish neuropeptide DRNFLRFamide (DF2) has previously been shown to increase the amplitude of excitatory post-synaptic potentials (EPSPs) in crayfish muscles by enhancing transmitter release from synaptic terminals [18]. This effect involves at least two types of kinase enzyme: one or more kinases which mediate the initial rise in EPSP amplitude, and protein kinase C (PKC) which prolongs the elevation in EPSP amplitude for several minutes [6,7]. The present investigation was aimed at identifying kinases that participate in the initial response. KN-62, an inhibitor of Ca2+/calmodulin-dependent protein kinase, delayed the rise in EPSP amplitude induced by DF2. The maximal response to the peptide occurred in about 40 min when KN-62 was present and in 15 min when the inhibitor was absent. KN-62 did not significantly alter EPSP amplitude by itself. KN-04, a structural analog of KN-62 which does not block Ca2+/CaM kinase activity, did not alter EPSP amplitude or the response to the neuropeptide. These data strongly suggest that Ca2+/CaM kinase participates in the initial increase in transmitter release.