Effect of K<SUP>+</SUP>-channel Blockers on the Muscarinic- and A<SUB>1</SUB>-adenosine- Receptor Coupled Regulation of Electrically Evoked Acetylcholine Release in the Rat Hippocampus

Effect of K<SUP>+</SUP>-channel Blockers on the Muscarinic- and A<SUB>1</SUB>-adenosine- Receptor Coupled Regulation of Electrically Evoked Acetylcholine Release in the Rat Hippocampus

<P> It was attempted to clarify the participation of K<SUP>+</SUP>-channels in the post-receptor mechanisms of the muscarinic and A<SUB>1</SUB>-adenosine receptor- mediated control of acetylcholine (ACh) release in the present study. Slices from the rat hippocampus were equilibrated with [<SUP>3</SUP>H]choline and the release of the labelled products was evoked by electrical stimulation (3 Hz, 5 V/cm, 2 ms, rectangular pulses), and the influence of various agents on the evoked tritium-outflow was investigated. Oxotremorine (Oxo, 0.1∼10 &#1356;M), a muscarinic agonist, and N<SUP>6</SUP>-cyclopentyladenosine (CPA, 1∼30 &#1356;M), a specific A<SUB>1</SUB>-adenosine agonist, decreased the ACh release in a dose-dependent manner, without affecting the basal rate of release. 4-aminopyridine (4AP), a specific A-type K<SUP>+</SUP>-channel blocker (1&#8764;100 &#1356;M), increased the evoked ACh release in a dose-related fashion, and the basal rate of release is increased by 3 and 100 &#1356;M. Tetraethylammonium (TEA), a non-specific K<SUP>+</SUP>-channel blocker (0.1&#8764;10 mM), increased the evoked ACh release in a dose-dependent manner without affecting the basal release. The effects of Oxo and CPA were not affected by 3 &#1356;M 4AP co-treatment, but 10 mM TEA significantly inhibited the effects of Oxo and CPA. 4AP (10 &#1356;M)- and TEA (10 mM)-induced increments of evoked ACh release were completely abolished in Ca<SUP>2+</SUP>-free medium, but these were recoverd in low Ca<SUP>2+</SUP> medium. And the effects of K<SUP>+</SUP>-channel blockers in low Ca<SUP>2+</SUP> medium were inhibited by Mg<SUP>2+</SUP> (4 mM) and abolished by 0.3 &#1356;M tetrodotoxin (TTX). These results suggest that the changes in TEA-sensitive potassium channel permeability and the consequent limitation of Ca<SUP>2+</SUP> influx are partly involved in the presynaptic modulation of the evoked ACh-release by muscarinic and A<SUB>1</SUB>-adenosine receptors of the rat hippocampus.