Summary
The question whether presynaptic α2-adrenoceptors regulating noradrenaline release in hippocampus directly couple to tetraethylammonium chloride (TEA) or α-dendrotoxin (α-DTX)-sensitive K+ channels was investigated. Hippocampal slices, prelabelled with [3H] noradrenaline, were superfused in the presence of (+)-oxaprotiline and electrically stimulated with 4 pulses delivered at 100 Hz, in order to avoid autoinhibition due to released noradrenaline.
TEA enhanced the evoked [3H]noradrenaline release in rabbit hippocampus in a concentration-dependent manner, yielding an approximately 4-fold increase at 30 mmol/l, whereas the spontaneous outflow of tritium was only slightly affected at this concentration. The α2-adrenoceptor agonist clonidine, at 10–100 nmol/l inhibited the evoked [3H]noradrenaline release between 77% and 96%. The inhibitory effect of the α2-agonist was distinctly diminished in the presence of 30 mmol/l TEA but was restored in low Ca2+/high Mg2+ buffer. Therefore, the diminution of the α2-agonist effect by TEA observed in experiments with normal Ca2+ can be explained by an increase of the Ca2+ availability for the release process due to the prolongation of action potentials. In rabbit hippocampus α-DTX (10–200 nmol/l) did neither affect the evoked release of [3H]noradrenaline nor its α2-agonist-induced modulation. However, in rat hippocampus α-DTX significantly increased the evoked transmitter release and diminished the effect of clonidine.
Taken together, the present data for the rabbit hippocampus exclude the possibility that activation of presynaptic α2-adrenoceptors inhibits depolarization-evoked [3H]noradrenaline release by inducing an outward K+ current through TEA- or α-DTX-sensitive K+ channels. However, there are species differences between the rabbit and the rat so that in the rat the α2-adrenoceptors could actually be coupled to K+ channels — provided that the release-enhancing properties of α-DTX do not account for the α2-antagonism observed.
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Correspondence to C. Allgaier at the above address
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Allgaier, C., Repp, H. & Hertting, G. Effect of K+ channel blockers on the α2-adrenoceptor-coupled regulation of electrically evoked noradrenaline release in hippocampus. Naunyn-Schmiedeberg's Arch Pharmacol 347, 14–20 (1993). https://doi.org/10.1007/BF00168766
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DOI: https://doi.org/10.1007/BF00168766