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PMID:12629219

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Citation

Hinds, HL, Goussakov, I, Nakazawa, K, Tonegawa, S and Bolshakov, VY (2003) Essential function of alpha-calcium/calmodulin-dependent protein kinase II in neurotransmitter release at a glutamatergic central synapse. Proc. Natl. Acad. Sci. U.S.A. 100:4275-80

Abstract

A significant fraction of the total calciumcalmodulin-dependent protein kinase II (CaMKII) activity in neurons is associated with synaptic connections and is present in nerve terminals, thus suggesting a role for CaMKII in neurotransmitter release. To determine whether CaMKII regulates neurotransmitter release, we generated and analyzed knockout mice in which the dominant alpha-isoform of CaMKII was specifically deleted from the presynaptic side of the CA3-CA1 hippocampal synapse. Conditional CA3 alpha-CaMKII knockout mice exhibited an unchanged basal probability of neurotransmitter release at CA3-CA1 synapses but showed a significant enhancement in the activity-dependent increase in probability of release during repetitive presynaptic stimulation, as was shown with the analysis of unitary synaptic currents. These data indicate that alpha-CaMKII serves as a negative activity-dependent regulator of neurotransmitter release at hippocampal synapses and maintains synapses in an optimal range of release probabilities necessary for normal synaptic operation.

Links

PubMed PMC153083 Online version:10.1073/pnas.0530202100

Keywords

Animals; Brain/enzymology; Brain/physiology; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Calcium-Calmodulin-Dependent Protein Kinases/deficiency; Calcium-Calmodulin-Dependent Protein Kinases/genetics; Calcium-Calmodulin-Dependent Protein Kinases/physiology; Excitatory Postsynaptic Potentials; Glutamic Acid/physiology; Hippocampus/physiology; In Situ Hybridization; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Neurotransmitter Agents/secretion; Restriction Mapping; Synapses/physiology

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


See also

References

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