| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2003: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Research Abstract |
This purpose of the present project was to investigate the interactions of noradrenaline and sevoflurane on inhibitory synaptic transmission mediated by GABA(A) receptors in the rat hippocampus. Pharmacologically isolated GABA(A) receptor-mediated IPSCs were recordedwith whole-cell patch clamp techniques in pyramidal neurons of the CA1 region of rat hippocampal slices. The actions of noradrenaline, noradrenaline analog, sevoflurane, and the interactions of these agents on the frequency and kinetics of spontaneous GABA(A) receptor-mediated IPSCs were studied. Noradrenaline (10 μM) caused an increase in the frequency of action potential-dependent sIPSCs. These effects were completely reversed by the addition of tetrodotoxin (1 μM), suggesting that noradrenaline produces the discharge of GABAergic interneurons innervating on pyramidal cells via adrenoceptors. Although sevoflurane (0.40 mM, 20 min) slightly depressed the amplitude of sIPSCs, sevoflurane significantly prolonged the decay ti
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me constant to 451.1±89.0% of control (n=9,P<0.001) without affecting the rise time. In addition, sevoflurane increased the frequency of sIPSCs up to three folds. However, pretreatment of cadmium, multiple Ca channel blocker, abolished sevoflurane effects on the frequency whereas the effects on the decay was still observed. Application of both noradrenaline and sevoflurane produced the significant increase of the IPSC frequency than that of noradrenaline alone or sevoflurane alone with prolonged decays. These results provide evidence that both agents have additive effects on GABAergic synaptic transmission at the central nervous system via different mechanisms.
We also investigated the effects of propofol on excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) and voltage responses in SG neurons by mechanical (pinch) stimuli applied to the skin using the newly developed in vivo patch-clamp technique. We found that propofol significantly prolonged the decay of IPSCs and decreased the frequency without affecting excitatory synaptic responses. In addition, propofol appeared to depress excitability of SG neurons. Less
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