Inhibitors of calmodulin and protein kinase C block different phases of hippocampal long-term potentiation.
The effects of a calmodulin (CaM) inhibitor, which does not influence Ca2+ fluxes (calmidazolium, RO-24571), and a new potent inhibitor of protein kinase C (K-252b) on long-term potentiation (LTP) were compared in hippocampal slices. Tetanic stimulation of the stratum radiatum during perfusion of calmidazolium (50 nM) failed to induce the characteristic post-tetanic and long-term increase in the magnitude of CA1-evoked responses. During perfusion with K-252b (50 nM) post-tetanic potentiation and initial LTP is expressed normally, but thereafter declines back to baseline with a 60 min delay. By themselves, the inhibitors had no significant effect on synaptic transmission in a non-tetanized control input. Our data are in line with current evidence from several laboratories that CaM- and protein kinase C (PKC)-dependent processes are involved in LTP and support the hypothesis that CaM mediates initiation and that PKC mediates mechanisms underlying the maintenance of LTP.
Reymann
K G
KG
Institute of Neurobiology and Brain Research, Academy of Sciences G.D.R., Magdeburg.
Brödemann
R
R
Kase
H
H
Matthies
H
H
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002147:Calmodulin / Q000502:physiology*; D002227:Carbazoles / Q000494:pharmacology*; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D026121:Indole Alkaloids; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains
D002147:Calmodulin; D002227:Carbazoles; D004791:Enzyme Inhibitors; D007093:Imidazoles; D026121:Indole Alkaloids; C031938:calmidazolium; C049985:staurosporine aglycone; D011493:Protein Kinase C