Korean J Physiol Pharmacol.  1998 Apr;2(2):147-154.

Effect of K+-channel blockers on the muscarinic- and A|1-adenosine-receptor coupled regulation of electrically evoked acetylcholine release in the rat hippocampus

• Yu BS
• Kim DK
• Choi BK

Abstract

It was attempted to clarify the participation of K+ channels in the post-receptor mechanisms of the muscarinic and A1-adenosine receptor-mediated control of acetylcholine (ACh) release in the present study. Slices from the rat hippocampus were equilibrated with (3H)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 micrometer), a muscarinic agonist, and N6-cyclopentyladenosine (CPA, 1~30 micrometer), a specific A1-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+-channel blocker (1~100 micrometer), increased the evoked ACh release in a dose-related fashion, and the basal rate of release is increased by 3 and 100 micrometer. Tetraethylammonium (TEA), a non-specific K+-channel blocker (0.1~10 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 micrometer 4AP co-treatment, but 10 mM TEA significantly inhibited the effects of Oxo and CPA. 4AP (10 micrometer- and TEA (10 mM)-induced increments of evoked ACh release were completely abolished in Ca2+-free medium, but these were recovered in low Ca2+ medium. And the effects of K+-channel blockers in low Ca2+ medium were inhibited by Mg2+ (4 mM) and abolished by 0.3 micrometer tetrodotoxin (TTX). These results suggest that the changes in TEA-sensitive potassium channel permeability and the consequent limitation of Ca2+ influx are partly involved in the presynaptic modulation of the evoked ACh-release by muscarinic and A1-adenosine receptors of the rat hippocampus.

Keyword

Tetraethylammonium; 4-aminopyridine; Muscarinic Receptor; A1-adenosine Receptor; Acetylcholine; Hippocampus

MeSH Terms

4-Aminopyridine
Acetylcholine*
Animals
Electric Stimulation
Hippocampus*
Muscarinic Agonists
Oxotremorine
Permeability
Potassium Channels
Rats*
Receptors, Muscarinic
Tea
Tetraethylammonium
Tetrodotoxin
4-Aminopyridine
Acetylcholine
Muscarinic Agonists
Oxotremorine
Potassium Channels
Receptors, Muscarinic
Tea
Tetraethylammonium
Tetrodotoxin