Calcium/calmodulin-dependent kinase II and long-term potentiation enhance synaptic transmission by the same mechanism.

TLDR

Ca(2+)-sensitive kinases are thought to play a role in long‑term potentiation (LTP). The study tested whether Ca2+/calmodulin‑dependent kinase II (CaM‑K II) contributes to synaptic potentiation by injecting a constitutively active form into CA1 pyramidal cells. The authors injected a truncated, constitutively active CaM‑K II into CA1 pyramidal cells and performed occlusion experiments to assess shared mechanisms with LTP. CaM‑K II injection increased EPSC amplitude, reduced synaptic failures, and enhanced spontaneous EPSCs, and its effects were occluded by prior LTP, indicating that CaM‑K II and LTP share the same underlying mechanism.

Abstract

Ca(2+)-sensitive kinases are thought to play a role in long-term potentiation (LTP). To test the involvement of Ca2+/calmodulin-dependent kinase II (CaM-K II), truncated, constitutively active form of this kinase was directly injected into CA1 hippocampal pyramidal cells. Inclusion of CaM-K II in the recording pipette resulted in a gradual increase in the size of excitatory postsynaptic currents (EPSCs). No change in evoked responses occurred when the pipette contained heat-inactivated kinase. The effects of CaM-K II mimicked several features of LTP in that it caused a decreased incidence of synaptic failures, an increase in the size of spontaneous EPSCs, and an increase in the amplitude of responses to iontophoretically applied alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate. To determine whether the CaM-K II-induced enhancement and LTP share a common mechanism, occlusion experiments were carried out. The enhancing action of CaM-K II was greatly diminished by prior induction of LTP. In addition, following the increase in synaptic strength by CaM-K II, tetanic stimulation failed to evoke LTP. These findings indicate that CaM-K II alone is sufficient to augment synaptic strength and that this enhancement shares the same underlying mechanism as the enhancement observed with LTP.