Parallel kinase cascades are involved in the induction of LTP at hippocampal CA1 synapses.
To identify the enzymes involved in the induction of N-methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP) at CA1 synapses of two-week-old rats we have tested various kinase inhibitors. Surprisingly, given the large body of evidence supporting a role for calcium/calmodulin-dependent protein kinase II (CaMKII) in LTP, inhibition of this enzyme did not affect the induction of LTP at this age. Similarly inhibition of protein kinase A (PKA) or protein kinase C (PKC) was also without effect. However, inhibition of CaMKII together with inhibition of either PKA or PKC fully blocked the induction of LTP. These experiments reveal, unexpectedly, the existence of two parallel kinase pathways, one involving CaMKII and the other PKA and PKC, either of which can fully support the induction of LTP, at this stage of development.
Wikström
Martin A
MA
MRC Centre for Synaptic Plasticity, Department of Anatomy, School of Medical Sciences, University Walk, Bristol BS8 1TD, UK.
Matthews
Paul
P
Roberts
Dewi
D
Collingridge
Graham L
GL
Bortolotto
Zuner A
ZA
D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000201:enzymology*; D017774:Long-Term Potentiation / Q000502:physiology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000096:biosynthesis*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000201:enzymology*
D004791:Enzyme Inhibitors; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases