FK506, a Ca2+/calmodulin-dependent phosphatase inhibitor, inhibits the induction of long-term potentiation in the rat hippocampus.
The effects of FK506, a Ca2+/calmodulin-dependent phosphatase 2B (calcineurin) inhibitor, on the synaptic potentials and long-term potentiation (LTP) were investigated, using extracellular recordings in the CA1 region of adult rat hippocampal slices. Bath application of FK506 (1-50 mu M) produced a dose-dependent and reversible inhibition on the field excitatory postsynaptic potentials. FK506 also showed an inhibitory effect on the induction of LTP evoked by theta-burst stimulation. Analyses of the fiber volley and paired-pulse facilitation revealed that FK506-induced effects were based on postsynaptic mechanisms. These results demonstrate that FK506 inhibits both the synaptic transmission and the LTP induction, and suggest that calcineurin plays a promoting role in the LTP processes in the hippocampus of adult rats.
First Department of Physiology, Okayama University Medical School, Japan.
Y F
YF
Lu
Y
Y
Hayashi
A
A
Moriwaki
K
K
Tomizawa
H
H
Matsui
D000818:Animals; D019703:Calcineurin; D002148:Calmodulin-Binding Proteins / Q000037:antagonists & inhibitors*; D004594:Electrophysiology; D006624:Hippocampus / Q000201:enzymology / Q000502:physiology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects; D016559:Tacrolimus / Q000494:pharmacology*
D002148:Calmodulin-Binding Proteins; D007166:Immunosuppressive Agents; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; D016559:Tacrolimus