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区GABA(A)受体介导的抑制性突触传递的影响。用全细胞膜片钳技术在大鼠海马脑片CA1区锥体神经元记录药物分离的GABA(A)受体介导的IPSCs。研究了去甲肾上腺素、去甲肾上腺素类似物、七氟醚对自发GABA(A)受体介导的IPSCs频率和动力学的作用及其相互作用。去甲肾上腺素(10μM)引起动作电位依赖的sIPSCs频率增加。这些效应可被河豚毒素(1μM)完全逆转，提示去甲肾上腺素通过肾上腺素受体产生支配锥体细胞的GABA能中间神经元的放电。虽然七氟醚(0.4 mM，20min)对…的幅度有轻微的抑制作用，但可显著延长sIPSC的衰变时间更多的Me常数为对照组(n=9，P&lt；0.001)的451.1±89.0%，而不影响上升时间。此外，七氟醚使sIPSCs的频率增加了三倍。然而，多钙通道阻滞剂镉可消除七氟醚对频率的影响，但对衰变的影响仍可观察到。同时应用去甲肾上腺素和七氟醚后，IPSC频率较单独使用去甲肾上腺素或七氟醚显著增加，且衰减时间延长。这些结果证明两种药物通过不同的机制对中枢神经系统GABA能突触传递具有相加作用。我们还利用最新发展的活体膜片钳技术研究了异丙酚对皮肤机械刺激(夹闭)对SG神经元兴奋性和抑制性突触后电流(EPSCs和IPSCs)和电压反应的影响。我们发现异丙酚显著延长了IPSCs的衰变，降低了IPSCs的频率，而不影响兴奋性突触反应。此外，异丙酚还可抑制SG神经元的兴奋性。较少

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