PMID- 10087064
OWN - NLM
STAT- MEDLINE
DCOM- 19990413
LR  - 20191023
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 19
IP  - 7
DP  - 1999 Apr 1
TI  - Adenylyl cyclase activation modulates activity-dependent changes in synaptic
      strength and Ca2+/calmodulin-dependent kinase II autophosphorylation.
PG  - 2500-10
AB  - Activation of the Ca2+- and calmodulin-dependent protein kinase II (CaMKII) and
      its conversion into a persistently activated form by autophosphorylation are
      thought to be crucial events underlying the induction of long-term potentiation
      (LTP) by increases in postsynaptic Ca2+. Because increases in Ca2+ can also
      activate protein phosphatases that oppose persistent CaMKII activation, LTP
      induction may also require activation of signaling pathways that suppress protein
      phosphatase activation. Because the adenylyl cyclase (AC)-protein kinase A
      signaling pathway may provide a mechanism for suppressing protein phosphatase
      activation, we investigated the effects of AC activators on activity-dependent
      changes in synaptic strength and on levels of autophosphorylated alphaCaMKII
      (Thr286). In the CA1 region of hippocampal slices, briefly elevating
      extracellular Ca2+ induced an activity-dependent, transient potentiation of
      synaptic transmission that could be converted into a persistent potentiation by
      the addition of phosphatase inhibitors or AC activators. To examine
      activity-dependent changes in alphaCaMKII autophosphorylation, we replaced
      electrical presynaptic fiber stimulation with an increase in extracellular K+ to 
      achieve a more global synaptic activation during perfusion of high Ca2+
      solutions. In the presence of the AC activator forskolin or the protein
      phosphatase inhibitor calyculin A, this treatment induced a LTP-like synaptic
      potentiation and a persistent increase in autophosphorylated alphaCaMKII levels. 
      In the absence of forskolin or calyculin A, it had no lasting effect on synaptic 
      strength and induced a persistent decrease in autophosphorylated alphaCaMKII
      levels. Our results suggest that AC activation facilitates LTP induction by
      suppressing protein phosphatases and enabling a persistent increase in the levels
      of autophosphorylated CaMKII.
FAU - Makhinson, M
AU  - Makhinson M
AD  - Interdepartmental Graduate Program for Neuroscience, University of California Los
      Angeles School of Medicine, Los Angeles, California 90095, USA.
FAU - Chotiner, J K
AU  - Chotiner JK
FAU - Watson, J B
AU  - Watson JB
FAU - O'Dell, T J
AU  - O'Dell TJ
LA  - eng
GR  - MH52876/MH/NIMH NIH HHS/United States
GR  - NS32521/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for
      Neuroscience
JID - 8102140
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 4.6.1.1 (Adenylyl Cyclases)
SB  - IM
MH  - Adenylyl Cyclases/*metabolism
MH  - Animals
MH  - Calcium-Calmodulin-Dependent Protein Kinase Type 2
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
MH  - Enzyme Activation
MH  - In Vitro Techniques
MH  - Long-Term Potentiation
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Phosphorylation
MH  - Receptors, N-Methyl-D-Aspartate/physiology
MH  - Signal Transduction/physiology
MH  - Stimulation, Chemical
MH  - Synaptic Transmission/*physiology
PMC - PMC6786061
EDAT- 1999/03/23 00:00
MHDA- 1999/03/23 00:01
CRDT- 1999/03/23 00:00
PHST- 1999/03/23 00:00 [pubmed]
PHST- 1999/03/23 00:01 [medline]
PHST- 1999/03/23 00:00 [entrez]
PST - ppublish
SO  - J Neurosci. 1999 Apr 1;19(7):2500-10.