| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1988: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1987: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Research Abstract |
The mechanism of the long-term potentiation of transmitter release (pre.-l.t.p.) induced by a tetanic stimulation to the pre-nerve fibres was examined in the bullfrog sympathetic ganglia. An increase in the quantal content of the fast excitatory postsynaptic potential (fast epsp) occurred during a gener-ation of the pre.-l.t.p. The frequency of the miniature epsps also increased after tetanic stimulation (33Hz, 5-30 sec). The magnitude of the short-term facilitation induced by a pair of stimulations (100 ms interval) in a low Ca^<2+> and high Mg^<2+> solution decreased during a generation of the pre.-l.t.p. A cal-cium ionophore, A-23187, increased the amplitude and the quantal content of fast epsps but reduced the short-term facilitation. On the other hand, a cal-cium chelating agent, quin-2 AM, reduced the amplitude and the quantal content of fast epsps. These results suggest that a sustained rise in the basal free Ca^<2+> in the pre-nerve fibres is necessary for a generation of the p
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re.-l.t.p.
Activators of the protein kinase C, phorbol-12-13 dibutyrate (PDB) and 1-oleoyl-2-acetyl-rac-glycerol (OAG), increased the amplitude and the quantal content of fast epsps and the frequency of miniature epsps. Under this condition, a tetanic stimulation to the pre-nerve fibres induced the pre.-l.t.p. The inhibitor of the protein kinase C, H-7, did not prevent a generation of the pre.-l.t.p. Staurosporine, which is known to block the protein kinase C, the cGMP- and the cgmp-dependent protein kinases and the myosin light chain kinase at a low concentration, did not prevent a generation of the pre.-l.t.p. These results suggest that those protein kinases do not play any role in a generation of the pre.-l.t.p. On the other hand, trifluoperazine, an inhibitor of the Ca/calmodulin(CaM) kinase II, prevented a generation of the per.-l.t.p. at the concentration of 1 uM. This suggests that the Ca/CaM kinase II may participate in a generation of the pre.-l.t.p. However, at present, the possibilit y that trifluoperazine blocks directly the membrane channels, e.g. Ca-channel, rather than the calmodulin can not be ruled out. Less
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