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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, Byung-Sik   (Department of Anesthesiology, College of Medicine, Chosun UniversityUU0001180  ); Kim, Do-Kyung   (Department of Pharmacology, Wonkwang University School of Medicine and Medicinal Resources Research Center of Wonkwang UniversityUU0001021  ); Choi, Bong-Kyu   (Department of Pharmacology, Wonkwang University School of Medicine and Medicinal Resources Research Center of Wonkwang UniversityUU0001021  );
  • 초록

    It was attempted to clarify the participation of $K^+-channels$ in the post-receptor mechanisms of the muscarinic and $A_1-adenosine$ 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, $0.1{\sim}10\;{\mu}M$ ), a muscarinic agonist, and $N^6-cyclopentyladenosine$ (CPA, $1{\sim}30\;{\mu}M$ ), a specific $A_1-adenosine$ 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 ( $1{\sim}100\;{\mu}M$ ), increased the evoked ACh release in a dose-related fashion, and the basal rate of release is increased by 3 and $100\;{\mu}M$ . Tetraethylammonium (TEA), a non-specific $K^+-channel$ blocker ( $0.1{\sim}10\;{\mu}M$ ), 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 $3\;{\mu}M$ 4AP co-treatment, but 10 mM TEA significantly inhibited the effects of Oxo and CPA. 4AP ( $10\;{\mu}M$ )- and TEA (10 mM)-induced increments of evoked ACh release were completely abolished in Ca^{2+}-free$ medium, but these were recoverd in low Ca^{2+}$ medium. And the effects of $K^+-channel$ blockers in low Ca^{2+}$ medium were inhibited by $Mg^{2+}$ (4 mM) and abolished by $0.3\;{\mu}M$ tetrodotoxin (TTX). These results suggest that the changes in TEA-sensitive potassium channel permeability and the consequent limitation of Ca^{2+}$ influx are partly involved in the presynaptic modulation of the evoked ACh-release by muscarinic and $A_1-adenosine$ receptors of the rat hippocampus.


  • 주제어

    Tetraethylammonium .   4-aminopyridine .   Muscarinic Receptor .   $A_1-adenosine$ Receptor .   Acetylcholine .   Hippocampus.  

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    2. 2001 "Influence of Strychnine on Catecholamine Release Evoked by Activation of Cholinergic Receptors from the Perfused Rat Adrenal Gland" The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology 5 (3): 243~251    
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