Klar Maximilian, Surges Rainer, Feuerstein Thomas J
Sektion Klinische Neuropharmakologie der Neurologischen Universitätsklinik Neurozentrum, Breisacher Strasse 64, 79106 Freiburg, Germany.
Naunyn Schmiedebergs Arch Pharmacol. 2003 Apr;367(4):422-5. doi: 10.1007/s00210-003-0707-6. Epub 2003 Mar 13.
Recent observations indicate the presence of hyperpolarization-activated cation channels (I(h) channels) in presynaptic terminals of central neurons, but their functional impact is still unclear. To investigate whether there are operative I(h) channels on presynaptic terminals of noradrenergic neurons, the effect of the I(h) channel blocker ZD7288 on the N-methyl-D-aspartate (NMDA)-evoked [3H]-noradrenaline release ([3H]-NA release) was tested. Neocortical slices of the rat, preloaded with [(3)H]-NA, were superfused in the presence of TTX (0.32 microM) and stimulated twice by addition of 300 microM NMDA. Application of 1 and 10 microM ZD7288 increased the NMDA-evoked [(3)H]-NA release by 29 and 44%, respectively, in the presence of 3 mM external K+. Elevation of external K+ to 6 mM significantly reduced the increasing effect of 10 microM ZD7288 to 15% only. Our results indicate the presence of I(h) channels on presynaptic terminals of noradrenergic neurons and suggest that presynaptic I(h) channels may attenuate transmitter release, at least under the present test conditions.
最近的观察结果表明，在中枢神经元的突触前终末存在超极化激活的阳离子通道（I(h)通道），但其功能影响仍不清楚。为了研究去甲肾上腺素能神经元的突触前终末是否存在起作用的I(h)通道，测试了I(h)通道阻滞剂ZD7288对N-甲基-D-天冬氨酸（NMDA）诱发的[3H]-去甲肾上腺素释放（[3H]-NA释放）的影响。预先用[(3)H]-NA加载的大鼠新皮质切片，在存在河豚毒素（TTX，0.32 microM）的情况下进行灌流，并通过添加300 microM NMDA刺激两次。在存在3 mM细胞外钾离子的情况下，应用1 microM和10 microM ZD7288分别使NMDA诱发的[(3)H]-NA释放增加了29%和44%。将细胞外钾离子浓度提高到6 mM仅将10 microM ZD7288的增加作用显著降低至15%。我们的结果表明去甲肾上腺素能神经元的突触前终末存在I(h)通道，并表明突触前I(h)通道可能会减弱递质释放，至少在当前的测试条件下是这样。
