Autonomous activity of CaMKII is only transiently increased following the induction of long-term potentiation in the rat hippocampus

I. Lengyel, K. Voss, M. Cammarota, K. Bradshaw, V. Brent, K. P S J Murphy, K. P. Giese, John A P Rostas*, T. V P Bliss

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

83 Citations (Scopus)

Abstract

A major role has been postulated for a maintained increase in the autonomous activity of CaMKII in the expression of long-term potentiation (LTP). However, attempts to inhibit the expression of LTP with CaMKII inhibitors have yielded inconsistent results. Here we compare the changes in CaMKII autonomous activity and phosphorylation at Thr 286 of αCaMKII in rat hippocampal slices using chemical or tetanic stimulation to produce either LTP or short-term potentiation (STP). Tetanus-induced LTP in area CA1 requires CaMKII activation and Thr 286 phosphorylation of αCaMKII, but we did not observe an increase in autonomous activity. Next we induced LTP by 10 min exposure to 25 mM tetraethyl-ammonium (TEA) or 5 min exposure to 41 mM potassium (K) after pretreatment with calyculin A. Exposure to K alone produced STP. These protocols allowed us to monitor temporal changes in autonomous activity during and after exposure to the potentiating chemical stimulus. In chemically induced LTP, autonomous activity was maximally increased within 30 s whereas this increase was significantly delayed in STP. However, in both LTP and STP the two-fold increase in autonomous activity measured immediately after stimulation was short-lived, returning to baseline within 2-5 min after re-exposure to normal ACSF. In LTP, but not in STP, the phosphorylation of αCaMKII at Thr 286 persisted for at least 60 min after stimulation. These results confirm that LTP is associated with a maintained increase in autophosphorylation at Thr 286 but indicate that a persistent increase in the autonomous activity of CaMKII is not required for the expression of LTP.

Original languageEnglish
Pages (from-to)3063-3072
Number of pages10
JournalEuropean Journal of Neuroscience
Volume20
Issue number11
DOIs
Publication statusPublished - Dec 2004
Externally publishedYes

Keywords

  • CaMKII
  • Long-term potentiation
  • Protein kinases
  • Protein phosphatases
  • Protein phosphorylation

ASJC Scopus subject areas

  • Neuroscience(all)

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