Transport of AMPA receptors during long-term potentiation is impaired in rats with hepatic encephalopathy.
Cognitive function is impaired in patients with hepatic encephalopathy. Learning ability is also impaired in rats with hepatic encephalopathy due to portacaval shunts. Long-term potentiation (LTP) in hippocampus, considered the basis of some forms of learning and memory, is impaired in rats with portacaval shunt. We analyzed the mechanisms by which LTP is impaired in these rats. In control rats, application of the tetanus to induce LTP increases phosphorylation of Thr286 of calcium-calmodulin dependent protein kinase II. This activates the kinase which phosphorylates the GluR1 subunit of AMPA receptors in Ser831 and induces its translocation to the post-synaptic densities. All these steps are completely prevented in rats with hepatic encephalopathy in which the tetanus does not induce phosphorylation of CaMKII or GluR1 nor translocation of this subunit to the post-synaptic membrane. This would explain the impairment in LTP in these rats.
Monfort
Pilar
P
Centro de Investigación Príncipe Felipe, Valencia, Spain.
Piedrafita
Blanca
B
Felipo
Vicente
V
D000818:Animals; D015153:Blotting, Western; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D000076122:Disks Large Homolog 4 Protein; D004558:Electric Stimulation; D006501:Hepatic Encephalopathy / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D000076122:Disks Large Homolog 4 Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D018091:Receptors, AMPA; C501449:Dlg4 protein, rat; C104722:glutamate receptor ionotropic, AMPA 2