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Free keywords:
Adenoviridae/genetics
Animals
CHO Cells
Cell Membrane/enzymology
Cricetinae
Cytosol/enzymology
Endothelium/*enzymology
Genetic Vectors
Hippocampus/*physiology
In Vitro Techniques
*Long-Term Potentiation/drug effects
Mice
Myristic Acid
Myristic Acids/metabolism/pharmacology
Neurons/*physiology
Nitric Oxide Synthase/genetics/*metabolism
Recombinant Fusion Proteins/metabolism
Synaptic Transmission
Transfection
Abstract:
Pharmacological studies support the idea that nitric oxide (NO) serves as a retrograde messenger during long-term potentiation (LTP) in area CA1 of the hippocampus. Mice with a defective form of the gene for neuronal NO synthase (nNOS), however, exhibit normal LTP. The myristoyl protein endothelial NOS (eNOS) is present in the dendrites of CA1 neurons. Recombinant adenovirus vectors containing either a truncated eNOS (a putative dominant negative) or an eNOS fused to a transmembrane protein were used to demonstrate that membrane-targeted eNOS is required for LTP. The membrane localization of eNOS may optimally position the enzyme both to respond to Ca2+ influx and to release NO into the extracellular space during LTP induction.