A role for endothelial NO synthase in LTP revealed by adenovirus-mediated inhibition and rescue.
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.
Kantor
D B
DB
Division of Biology 216-76, California Institute of Technology, Pasadena, CA 91125, USA. schumane@cco.caltech.edu
Lanzrein
M
M
Stary
S J
SJ
Sandoval
G M
GM
Smith
W B
WB
Sullivan
B M
BM
Davidson
N
N
Schuman
E M
EM
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D016466:CHO Cells; D002462:Cell Membrane / Q000201:enzymology; D006224:Cricetinae; D003600:Cytosol / Q000201:enzymology; D004727:Endothelium / Q000201:enzymology*; D005822:Genetic Vectors; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects; D051379:Mice; D019814:Myristic Acid; D009227:Myristic Acids / Q000378:metabolism / Q000494:pharmacology; D009474:Neurons / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D009435:Synaptic Transmission; D014162:Transfection
D009227:Myristic Acids; D011993:Recombinant Fusion Proteins; D019814:Myristic Acid; C017418:alpha-hydroxymyristic acid; D019001:Nitric Oxide Synthase