Abstract
Recent observations indicate the presence of hyperpolarization-activated cation channels (Ih channels) in presynaptic terminals of central neurons, but their functional impact is still unclear. To investigate whether there are operative Ih channels on presynaptic terminals of noradrenergic neurons, the effect of the Ih 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 [3H]-NA, were superfused in the presence of TTX (0.32 µM) and stimulated twice by addition of 300 µM NMDA. Application of 1 and 10 µM ZD7288 increased the NMDA-evoked [3H]-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 µM ZD7288 to 15% only. Our results indicate the presence of Ih channels on presynaptic terminals of noradrenergic neurons and suggest that presynaptic Ih channels may attenuate transmitter release, at least under the present test conditions.
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This work was supported by the Deutsche Forschungsgemeinschaft (SFB 505, TPC8).
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M.K. and R.S. contributed equally to this work
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Klar, M., Surges, R. & Feuerstein, T.J. Ih channels as modulators of presynaptic terminal function: ZD7288 increases NMDA-evoked [3H]-noradrenaline release in rat neocortex slices. Naunyn-Schmiedeberg's Arch Pharmacol 367, 422–425 (2003). https://doi.org/10.1007/s00210-003-0707-6
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DOI: https://doi.org/10.1007/s00210-003-0707-6