Induction of stable long-term potentiation in the presence of the protein kinase C antagonist staurosporine

Michelet, Dominique; Bittar, Philippe; Boddeke, Hendrik W.G.M.

doi:10.1016/0304-3940(92)90126-r

Cited by 27 publications

(17 citation statements)

References 26 publications

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“…Sustained potentiation was obtained in pathway $2 >30 min after K-252a washout (27-+4%), indicating that the ability of K-252a to block LTP induction is reversible. Similar to other studies (Muller et al 1992), staurosporine (2-4 i~i) applied 20 min before until 20 min after HFS reduced the magnitude of LTP (16-4%, n=3; Fig. 1B) compared with LTP in control slices (41-+5%, n=8, P<O.05).…”

Section: Protein Kinase Inhibitors Block Ltp Induction Without Affectsupporting

confidence: 88%

“…It has been suggested that one of the roles of protein kinases in LTP induction is to modulate NMDA receptor activity during HFS (Ben-Ari 1992; Muller et al 1992). To determine whether the ability of K-252a to block LTP was by attenuating NMDA receptor activity, we monitored the effect of K-252a on NMDA receptor EPSPs.…”

Section: K-252a Does Not Affect Nmda Receptor-mediated Synaptic Transmentioning

confidence: 99%

“…In addition, H-7 has been reported to have nonspecific (kinase-independent) effects on NMDA receptor activity (Amador and Dani 1991 ). More recent studies (Reymann et al 1990;Matthies et al 1991;Muller et al 1992) have utilized a new class of protein kinase inhibitors (K-252b and staurosporine), which are potent, membranepermeable, broad-range kinase inhibitors that do not possess the reported nonspecific affects of H-7. Although consistent results were obtained indicating that protein kinase activities are required during LTP induction (Denny et al 1990;Reymann et al 1990, Matthies et al 1991Muller et al 1992), there have been conflicting results on the effects of these inhibitors on LTP expression (see Denny et al 1990;Matthies et al 1991).…”

Section: Introductionmentioning

confidence: 99%

“…More recent studies (Reymann et al 1990;Matthies et al 1991;Muller et al 1992) have utilized a new class of protein kinase inhibitors (K-252b and staurosporine), which are potent, membranepermeable, broad-range kinase inhibitors that do not possess the reported nonspecific affects of H-7. Although consistent results were obtained indicating that protein kinase activities are required during LTP induction (Denny et al 1990;Reymann et al 1990, Matthies et al 1991Muller et al 1992), there have been conflicting results on the effects of these inhibitors on LTP expression (see Denny et al 1990;Matthies et al 1991). Wang and Feng (1992) were successful in demonstrating that the postsynaptic injection of a combination of PKC inhibitors, the pseudosubstrate inhibitory peptide PKC ~9--31 and polymixin B, specifically attenuated potentiated pathways, whereas other studies have found that the postsynaptic injection of H-7 , PKC19_31, or a peptide inhibitor of CaMKII (CaiKII273..3o2) did not impact on LTP expression (Malinow et al 1989).…”

Section: Introductionmentioning

confidence: 99%

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A critical period of protein kinase activity after tetanic stimulation is required for the induction of long-term potentiation.

Huber¹,

Mauk²,

Thompson³

1995

Learn. Mem.

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A critical period of protein kinase activity required for the induction of long-term potentiation (LTP) was determined in area CA1 of hippocampal slices using the broad-range and potent protein kinase inhibitors K-252a and staurosporine. As reported previously, K-252a and staurosporine blocked LTP induction when applied before, during, and after high-frequency stimulation (HFS). In contrast, K-252a did not block LTP when applied only before and during HFS and washed out immediately after HFS. K-252a and staurosporine both attenuated LTP magnitude when applied immediately after or as late as 5 min after HFS. However, K-252a applications beginning 30-45 rain after HFS did not affect LTP expression significantly. K-252a had no detectable effect on isolated N-methyl-v-aspartate (NMDA) receptor-mediated EPSPs but significantly inhibited the in situ phosphorylation of specific hippocampal proteins (synapsin I, MARCKS, and B-50). In addition, K-252a attenuated 4~-phorbol-12,13-dibutyrate (PDBu)-enhanced synaptic transmission. Our results indicate that there is a critical period of protein kinase activity required for LTP induction that extends for ---20 min after HFS. In addition, our results suggest that protein kinase activity during and immediately after HFS is not sufficient for LTP induction. These results provide new information about the mechanisms that underlie LTP induction and expression and aCorresponding author.provide evidence for persistent and/or Ca2+-independent protein kinase activity involvement in LTP

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Section: Protein Kinase Inhibitors Block Ltp Induction Without Affectsupporting

confidence: 88%

Section: K-252a Does Not Affect Nmda Receptor-mediated Synaptic Transmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A critical period of protein kinase activity after tetanic stimulation is required for the induction of long-term potentiation.

Huber¹,

Mauk²,

Thompson³

1995

Learn. Mem.

View full text Add to dashboard Cite

show abstract

“…This suggests that the molecular mechanisms bidirectionally regulating synaptic transmission involve a constitutively active PKC, perhaps PKM, although there may be other forms of autonomous PKC to be characterized in future studies. In addition, however, staurosporine and its analog K252a, inhibitors acting on the catalytic domain of many kinases, including conventional PKCs and CaM-kinase II (Ward and O'Brian, 1992;Huber et al, 1995), have been reported not to reverse LTP maintenance (Denny et al, 1990b;Muller et al, 1992; Huber et al, 1995) (but see Matthies et al, 1991). These results appear to contradict the experiments with H7 and chelerythrine.…”

Section: Bidirectional Regulation Of Autonomous Pkc In the Maintenancmentioning

confidence: 97%

Bidirectional Regulation of Protein Kinase Mζ in the Maintenance of Long-Term Potentiation and Long-Term Depression

1996

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Long-term potentiation (LTP) and long-term depression (LTD) are persistent modifications of synaptic efficacy that may contribute to information storage in the CA1 region of the hippocampus. Persistently enhanced phosphorylation has been implicated in the maintenance phase of LTP. This hypothesis is supported by our previous observation that protein kinase M (PKM), the constitutively active catalytic fragment of a single protein kinase C isoform (PKC), increases in LTP maintenance. In contrast, dephosphorylation may be important in LTD maintenance, because phosphatase inhibitors reverse established LTD, in addition to blocking its induction. Because phosphorylation is determined by a balance of phosphatases and kinases, both increases in phosphatase activity and decreases in kinase activity could contribute to LTD. We now report that the reduction of protein kinase activity by H7, as well as selective inhibition of PKC by chelerythrine, mimics and occludes the maintenance phase of homosynaptic LTD in rat hippocampal slices. Conversely, saturated LTD occludes the synaptic depression caused by chelerythrine. Biochemical analysis demonstrates a decrease of PKM, as well as PKCs ␥ and ⑀, in LTD maintenance and a concomitant loss of constitutive PKC activity. LTD and the downregulation of PKM are prevented by NMDA receptor antagonists and Ca 2ϩ -dependent protease inhibitors. Both LTD and the downregulation of PKM are reversible by high-frequency afferent stimulation. Our findings indicate that the molecular mechanisms of LTP and LTD maintenance are inversely related through the bidirectional regulation of PKC.

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Staurosporine but not chelerythrine inhibits regeneration in hippocampal organotypic cultures

Toni¹,

Stoppini²,

Michelet³

1997

Synapse

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A mechanical lesion in hippocampal organotypic cultures is followed by a recovery process involving scar formation, sprouting of fibres and formation of new functional synapses. Here we tested the effect of staurosporine and chelerythrine, two protein kinase C (PKC) inhibitors, on this lesion-induced neurite outgrowth of Shaffer collaterals. At a concentration of 1 microM, staurosporine delayed functional recovery assessed by measuring synaptic field potentials across the lesion, without altering synaptic transmission on nonlesioned cultures. Immunostaining carried out by using antibodies directed against neurofilament proteins showed that there was a marked reduction in the number of regenerating fibres crossing the lesion. In contrast to this, chelerythrine (50 microM) did not prevent functional recovery, although it affected synaptic transmission and plasticity at this concentration. We conclude that the inhibition of sprouting produced by staurosporine is independent of its blockade of PKC-mediated phosphorylation mechanisms.

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Induction of stable long-term potentiation in the presence of the protein kinase C antagonist staurosporine

Cited by 27 publications

References 26 publications

A critical period of protein kinase activity after tetanic stimulation is required for the induction of long-term potentiation.

A critical period of protein kinase activity after tetanic stimulation is required for the induction of long-term potentiation.

Bidirectional Regulation of Protein Kinase Mζ in the Maintenance of Long-Term Potentiation and Long-Term Depression

Staurosporine but not chelerythrine inhibits regeneration in hippocampal organotypic cultures

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