Inhibition of phosphatase 2B prevents expression of hippocampal long-term potentiation.
The induction of long-term potentiation (LTP) in the CA1 region of the hippocampus is mediated by N-methyl-D-aspartate (NMDA) receptor-coupled calcium influx. In addition, calcium/calmodulin (CaM) has been demonstrated to play an essential role in the induction process. In the present study, a possible role of CaM-dependent phosphatase (phosphatase 2B, PP-2B, calcineurin) in the LTP process was examined by intracellular recordings in apical dendrites of CA1 pyramidal cells of adult guinea-pigs. In dendrites in which cypermethrin, a potent and specific inhibitor of PP-2B (IC50 40 pM), was intracellularly applied, tetanization generated only short-term increases (15-30 min) of excitatory responses. In the intracellular presence of allethrin, a weak inhibitor of PP-2B, LTP expression was not affected. These findings demonstrate that activation of PP-2B is a necessary condition for the expression of LTP in CA1 pyramidal cell dendrites.
Wang
J H
JH
Department of Pharmacology, University of New York, Health Science Center at Brooklyn, 11203.
Stelzer
A
A
D000487:Allethrins / Q000494:pharmacology; D000818:Animals; D019703:Calcineurin; D002148:Calmodulin-Binding Proteins / Q000037:antagonists & inhibitors*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D011722:Pyrethrins / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects
D000487:Allethrins; D002148:Calmodulin-Binding Proteins; D011722:Pyrethrins; C017160:cypermethrin; D004533:Egtazic Acid; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D004121:Dimethyl Sulfoxide