Nakanishi, Keiko, Fan Zhang, Douglas A. Baxter, Arnold Eskin, and John H. Byrne. Role of calcium-calmodulin–dependent protein kinase II in modulation of sensorimotor synapses in Aplysia. J. Neurophysiol. 78: 409–416, 1997. The Ca2+-calmodulin–dependent protein kinase II (CaMKII) inhibitor, {1-[N,O - bis(5 - isoquinolinesulfonyl) - N - methyl - L - tyrosyl] - 4 - phenylpiper azine} (KN-62), was used to investigate the role of CaMKII in synaptic transmission and serotonin (5-HT)-induced facilitation in Aplysia. Application of KN-62 (10 μM) by itself increased the amplitude of excitatory postsynaptic potentials (EPSPs) at sensorimotor synapses in pleural-pedal ganglia. Moreover, in the presence of KN-62, 5-HT–induced short-term facilitation was attenuated. Application of KN-62 by itself slightly increased the duration of action potentials in isolated sensory neuron somata but did not block spike broadening produced by 5-HT. KN-62 had no effect on excitability of isolated sensory neuron somata nor did it block 5-HT–induced enhancement of excitability. These results indicate that the attenuation of short-term facilitation by KN- 62 is not due to modulation of the membrane currents contributing to 5-HT–induced spike broadening or enhancement of excitability. Rather, these data are consistent with the hypothesis that CaMKII contributes to the regulation of sensorimotor connections and that it has a role in spike-duration–independent processes contributing to short-term facilitation.
Functional determinants in the autoinhibitory domain of calcium/calmodulin-dependent protein kinase II. Role of His282 and multiple basic residues.