The signaling and transmission of pain and synaptic plasticity : in vivo patch clamp analysis of synaptic transmission at dorsal horn neurons in the rat spinal cord.

本研究旨在探讨去甲肾上腺素和七氟醚对大鼠海马GABA（A）受体介导的抑制性突触传递的相互作用。用全细胞膜片钳技术在大鼠海马脑片CA1区锥体神经元上记录GABA（A）受体介导的IPSC。研究了去甲肾上腺素、去甲肾上腺素类似物、七氟烷的作用以及这些药物对自发GABA（A）受体介导的IPSC的频率和动力学的相互作用。去甲肾上腺素（10 μM）引起动作电位依赖性sIPSC频率增加。加入河豚毒素（1 μM）可完全逆转这些效应，表明去甲肾上腺素通过肾上腺素受体产生支配锥体细胞的GABA能中间神经元放电。虽然七氟烷（0.40 mM，20 min）轻微抑制sIPSC的振幅，但七氟烷显著延长了sIPSC的衰减时间。 关于我们 在不影响上升时间的情况下，使平均上升时间恒定为对照的451.1±89.0%（n=9，P<0.001）。此外，七氟烷使sIPSC的频率增加了3倍。然而，预处理镉，多种钙通道阻滞剂，取消七氟烷对频率的影响，而对衰减的影响仍然观察到。去甲肾上腺素和七氟醚的应用产生的IPSC频率显着增加比单独去甲肾上腺素或七氟醚单独延长衰减。这些结果提供了证据表明，这两种药物通过不同的机制在中枢神经系统GABA能突触传递的叠加效应。我们还研究了丙泊酚对SG神经元的兴奋性和抑制性突触后电流（EPSC和IPSC）和电压反应的影响，通过机械（捏）刺激施加到皮肤使用新开发的在体膜片钳技术。我们发现，异丙酚显着延长衰减的IPSC和减少的频率，而不影响兴奋性突触反应。此外，异丙酚似乎抑制SG神经元的兴奋性。少

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 … More 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