The translocation and involvement of protein kinase C in mossy fiber-CA3 long-term potentiation in hippocampus of the rat brain.
The detailed mechanisms underlying long-term potentiation (LTP) are not known. In hippocampal CA1, translocation of protein kinase C (PKC) activity from cytosol to membrane and subsequent phosphorylation of growth associated protein (GAP)-43 have been demonstrated to be critical events for the maintenance phase of LTP. LTP in mossy fiber (MF)-CA3 pathway and the Schaffer collateral/commissural (SC)-CA1 pathway differ in a number of ways: SC-CA1 LTP depends on NMDA receptors while MF-CA3 LTP does not, and SC-CA1 LTP is primarily postsynaptic while MF-CA3 LTP is primarily presynaptic. The role of PKC in MF-CA3 LTP has not been studied. We investigated the role of PKC in CA3 and show that PKC inhibitors prevent LTP, but that PKC activators produce a reversible synaptic potentiation, indicating that PKC activation is an essential but not sufficient component of LTP in CA3. Then using antibodies against specific PKC isozymes we have determined the membrane vs. cytosolic distribution of various PKC isozymes in slices subjected to low or tetanic stimulation, or perfused with phorbol esters (PDAc). Compared with control, LTP and PDAc slices show greater PKC-alpha and -epsilon immunoreactivity in the membrane fraction, indicating that both LTP and phorbol ester treatment induce translocation of PKC-alpha and -epsilon from cytosol to membrane. However, with PKC-beta and PKC-gamma the only detectable translocation from cytosol to membrane was in the phorbol ester-treated slices. Thus, while phorbol ester treatment causes translocation of PKC-alpha, -beta, -gamma and -epsilon, the only detectable translocation associated with CA3 LTP is that of PKC-alpha and -epsilon.
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Wadsworth Center for Laboratories and Research, New York State Department of Health, Albany, USA.
Madelian
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Carpenter
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D000704:Analysis of Variance; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D003600:Cytosol / Q000201:enzymology; D004558:Electric Stimulation; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D008566:Membranes / Q000201:enzymology; D009412:Nerve Fibers / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013347:Subcellular Fractions / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism / Q000502:physiology
D007527:Isoenzymes; D011493:Protein Kinase C